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Archive for the ‘Gene Therapy Doctor’ Category

Coach and Little Grace: Mother of child with Down Syndrome gets life-changing phone call – WVTM13

Eighteen years ago, former Alabama football coach Gene Stallings made a difference in the life of a grieving woman and her beautiful newborn.It's a story about love and compassion, a story that has not been told until now.This is the story of The Coach and Little Grace:Her heart was heavy on Mother's Day 2002.Laura Davis was depressed and confused as her first child slept at her side.Was she crazy to feel so sad? So hopeless? After all, her daughter Grace was a mere 14 days old. Laura Davis was supposed to be happy.As Grace slept, Laura asked God for answers. How was she supposed to care for a child with Down Syndrome? How was she supposed to see the future as her child had just been diagnosed with two holes in her heart? How was she supposed to have hope when her doctor told her that little Grace would never walk, talk or read?Her husband was doing his residency in Columbus, Ohio, and while Chris was working hard, Laura cried. She was overwhelmed. She missed her hometown of Vestavia Hills. She missed talking about life and Bama football with her friends.And getting out of bed? It just wasn't happening.The phone rang, and Laura took a deep breath, inhaling tears that had fallen from her eyes."Hello," said Laura."Hello, Laura, this is Gene Stallings. I wanted to call to wish you a Happy Mother's Day."Laura's heart jumped.Was it really THE Gene Stallings? The head coach of her beloved Crimson Tide?Why in the world was Gene Stallings calling Laura Davis, who was in Columbus, Ohio?"I also want to congratulate you on your newborn, Grace," the Tide coach said.How in the world did Coach Stallings know about Grace?The two exchanged pleasantries, and then Stallings revealed why he was really calling: To give Laura Davis hope. To get her out of bed.The coach proposed a question to Laura:"What is the one thing that you want for little Grace? You want her to someday go to heaven, right?""Of course," Laura replied.And then came just one of many bits of advice that the coach offered up:"Well, Laura, Grace has a one-way ticket because God loves her and so do you," he said. "You may not know this right now, but you are in for the ride of your life. You will never stop loving little Grace."And another piece of advice from the coach:"If the Lord asked me if I would rather have had John Mark the way he is or had him as a 'normal' child, I would tell Him that I would rather have had Johnny just the way he is."Coach Stallings said "goodbye" and hung up the phone.The tears in Laura's eyes returned. But this time they were happy tears. She had chill bumps.Little Grace remained next to her, asleep.We never know when that moment might come, but on Mother's Day 2002 that moment came for Laura Davis.She closed her eyes and prayed, promising God that she was going to make the most of Grace's life and offer her daughter every ounce of love that she could muster.And suddenly, good things started to happen:The two holes in Grace's heart closed on their own.Grace smiled.Physical therapy began, then speech therapy.Laura and Chris would move back to Vestavia Hills as Grace turned two. Years of hard work followed. Reading, writing, speaking.Vestavia Hills' special education teacher Jennifer Greer came into their lives and Grace blossomed as a cheerleader, a student and a friend.God was good.And now for the cherry on top:Three days ago, Grace Davis, the girl who was doubted, mocked, and given little chance to live a fulfilling life, graduated from Vestavia Hills High School. Grace will enter Auburn's "Eagles" program this fall. Yes, 18 years after doctors doubted her, Grace Davis will be going to college.Chris and Laura Davis are enjoying life in Vestavia Hills. Chris is an ENT doctor, and their sons Jack and Will are growing fast.Laura tells me that she will never forget Mother's Day 2002, the day that she received an unexpected phone call not from a football legend, but rather from the father of a Down Syndrome child.It was a phone call that motivated Laura to get of bed and look to the future one that ended up being more amazing than she could have ever imagined.And now you know the story of The Coach and Little Grace.A story with a happy ending!

Eighteen years ago, former Alabama football coach Gene Stallings made a difference in the life of a grieving woman and her beautiful newborn.

It's a story about love and compassion, a story that has not been told until now.

This is the story of The Coach and Little Grace:

Her heart was heavy on Mother's Day 2002.

Laura Davis was depressed and confused as her first child slept at her side.Was she crazy to feel so sad? So hopeless? After all, her daughter Grace was a mere 14 days old. Laura Davis was supposed to be happy.

As Grace slept, Laura asked God for answers. How was she supposed to care for a child with Down Syndrome? How was she supposed to see the future as her child had just been diagnosed with two holes in her heart? How was she supposed to have hope when her doctor told her that little Grace would never walk, talk or read?

Her husband was doing his residency in Columbus, Ohio, and while Chris was working hard, Laura cried. She was overwhelmed. She missed her hometown of Vestavia Hills. She missed talking about life and Bama football with her friends.

And getting out of bed? It just wasn't happening.

The phone rang, and Laura took a deep breath, inhaling tears that had fallen from her eyes.

"Hello," said Laura.

"Hello, Laura, this is Gene Stallings. I wanted to call to wish you a Happy Mother's Day."

Laura's heart jumped.

Was it really THE Gene Stallings? The head coach of her beloved Crimson Tide?

Why in the world was Gene Stallings calling Laura Davis, who was in Columbus, Ohio?

"I also want to congratulate you on your newborn, Grace," the Tide coach said.

How in the world did Coach Stallings know about Grace?

The two exchanged pleasantries, and then Stallings revealed why he was really calling: To give Laura Davis hope. To get her out of bed.

The coach proposed a question to Laura:

"What is the one thing that you want for little Grace? You want her to someday go to heaven, right?"

"Of course," Laura replied.

And then came just one of many bits of advice that the coach offered up:

"Well, Laura, Grace has a one-way ticket because God loves her and so do you," he said. "You may not know this right now, but you are in for the ride of your life. You will never stop loving little Grace."

And another piece of advice from the coach:

"If the Lord asked me if I would rather have had John Mark the way he is or had him as a 'normal' child, I would tell Him that I would rather have had Johnny just the way he is."

Coach Stallings said "goodbye" and hung up the phone.

The tears in Laura's eyes returned. But this time they were happy tears. She had chill bumps.

Little Grace remained next to her, asleep.

We never know when that moment might come, but on Mother's Day 2002 that moment came for Laura Davis.

She closed her eyes and prayed, promising God that she was going to make the most of Grace's life and offer her daughter every ounce of love that she could muster.

And suddenly, good things started to happen:

The two holes in Grace's heart closed on their own.

Grace smiled.

Physical therapy began, then speech therapy.

Laura and Chris would move back to Vestavia Hills as Grace turned two. Years of hard work followed. Reading, writing, speaking.

Vestavia Hills' special education teacher Jennifer Greer came into their lives and Grace blossomed as a cheerleader, a student and a friend.

God was good.

And now for the cherry on top:

Three days ago, Grace Davis, the girl who was doubted, mocked, and given little chance to live a fulfilling life, graduated from Vestavia Hills High School.

Vestavia Hills City Schools

Grace will enter Auburn's "Eagles" program this fall. Yes, 18 years after doctors doubted her, Grace Davis will be going to college.

Chris and Laura Davis are enjoying life in Vestavia Hills. Chris is an ENT doctor, and their sons Jack and Will are growing fast.

Laura tells me that she will never forget Mother's Day 2002, the day that she received an unexpected phone call not from a football legend, but rather from the father of a Down Syndrome child.

It was a phone call that motivated Laura to get of bed and look to the future one that ended up being more amazing than she could have ever imagined.

And now you know the story of The Coach and Little Grace.

A story with a happy ending!

See more here:
Coach and Little Grace: Mother of child with Down Syndrome gets life-changing phone call - WVTM13

The Rundown: May 22, 2020 – Multiversity Comics

Welcome back to The Rundown, our daily breakdown on comic news stories we missed from the previous day. Have a link to share? Email our team at rundown@multiversitycomics.com.

In case you missed it, we got an exclusive preview of Sera and the Royal Stars #7.

Nathan W. Pyles Strange Planet will be getting a subscription box from Culturefly, The Pop Insider reports. Fans will be able to get exclusive merchandise inspired by the comic as part of this new subscription box. Each box includes a vinyl figure, an exclusive comic on a canvas print, and five to seven additional items featuring the creatures. The subscription box will launch on June 1.

Via Bleeding Cool, Doctor Who fans were treated to a special comic strip written by James Peaty, illustrated by Mike Collins, and narrated by Richard Ashton, in which fans find out more about Danny Pink. Its unclear when the next series of Doctor Who will premiere, although the show will return in the next year with the special Revolution of the Daleks.

Variety reports that Nick Jonas and Lawrence Fishburne are set to star in AGC Studios The Blacksmith, based on the graphic novel from Kickstart Comics by Malik Evans and Richard Sparkman. Pierre Morel (Taken) will direct from a screenplay adapted by Ben Ripley (Flatliners). Jonas will play Wes Loomis, a go-to weapons expert for the intelligence community, who goes on the run after his lab is destroyed and colleagues are murdered. Fishburne will play Mather, a retired blacksmith, and Loomiss mentor. With the aid of a CIA analyst named Noelle Hazlitt, the trio will embark on a journey that keeps this improbable pair one step ahead of their pursuers in a breathless, action-filled thriller. Production on the film will begin later in 2020.

Via Comicbook.com, Cartoon Network announced that We Bare Bears: The Movie will officially release for purchase on digital platforms on June 8, 2020. This is the first movie for the We Bare Bears franchise, which follows three talking bears as they explore life in the woods and city. In addition to the release date, Cartoon Network has also revealed a poster and trailer. The movie will depict the bears as they make their way to Canada after being chased from their home by antagonist, Agent Trout. Eric Edelstein, Demetri Martin, and Bobby Moynihan star in the movie as the bears Grizz, Ice, and Panda. Agent Trout is voiced by Marc Evan Jackson and many of the shows guest stars will also be featured in the movie. We Bare Bears: The Movie is scheduled to release for purchase on digital platforms for $14.99 on June 8, 2020.

Netflix has released the official trailer for The Old Guard, based on the comic by Greg Rucka and Leandro Fernandez. Like the comic, the movie follows a group of immortal soldiers led by Andy, played by Charlize Theron, who must fight to keep their immortality a secret, or otherwise see their gifts exploited. The film will begin streaming on Netflix on July 10, 2020. You can check out the trailer here.

Deadline reports that Sony has hired Marc Guggenheim to write a script for Jackpot, another installment in the larger Spider-Man Cinematic universe following the Venom franchise, and Jared Letos Morbius. In the comics, Jackpot is Sara Ehret, a scientist, who, while pregnant, is doing gene therapy research and is exposed to Lot 777, a virus that rewrites the DNA in her cells. She becomes imbued with superhuman strength and takes on the name Jackpot. Morbius is scheduled to be released on March 19, 2021, while Venom: Let There Be Carnage is set to hit theaters June 25, 2021.

TV Line reports that ABC has renewed 13 shows on their current lineup, including Stumptown. The TV show is based on the comic book series from creators Greg Rucka and Matthew Southworth, and follows Dex, an army vet turned private detective. Season 1 premiered in September. Its unknown when production will begin on season 2 of Stumptown.

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The Rundown: May 22, 2020 - Multiversity Comics

CAR T-Cell Therapy a ‘Really Exciting’ Development in Treatment of Lymphomas – Curetoday.com

The evolution of CAR T-cell therapy has been an exciting development for the treatment of all lymphomas, including mantle cell lymphoma, according to Dr. Ian Flinn.

BY Dr. Ian Flinn

The evolution of CAR T-cell therapy has been an exciting development for the treatment of all lymphomas, including mantle cell lymphoma, according to Dr. Ian Flinn.

In an interview with CURE, Flinn, the director of lymphoma research at Sarah Cannon Research Institute, discussed the use of CAR T-cells to treat lymphomas, as well as how the ZUMA-2 trial is shaping up to influence the treatment of patients with mantle cell lymphoma.

Transcription:

CURE: I'm curious about the ZUMA-2 trial. I know that you're an investigator on that trial. So, if you could talk a little bit about the drug, what it targets, how it works in the body and where things are with that study so far.

Flinn: ZUMA-2 is a clinical trial looking at a CAR T-cell product that targets CD19, which is an antigen on a lot of lymphomas, in this case mantle cell lymphoma, in patients who have had multiple prior therapies for their mantle cell lymphoma, and who are really no longer responding.

So, in this trial, we administered CAR T-cells to these patients. And after giving them some what's called lymphodepleting chemotherapy, and then infuse the CAR T-cells into the patients, we saw a really pretty remarkable outcome.

First (let me offer) a little bit about what a CAR T-cell is. Its a white blood cell, a lymphocyte, that is harvested from the blood of a patient. It's then sent to a central manufacturing facility, where a gene is inserted into the lymphocyte to have the lymphocyte activate as well as target the lymphoma. In this case, it's targeting that antigen called CD19, that's present on most B cell lymphomas and most all the mantle cell lymphoma, many other types of lymphoma as well.

So, it's a really exciting development in the treatment of all lymphomas and in certain forms of leukemia. A similar CAR T-cell product had previously been shown to be very effective in patients with an aggressive form of lymphoma, known as large cell lymphoma. And studies in that patient population led to the approval of CAR T-cells for patients with diffuse large B-cell lymphoma, who also similarly were not really responding to any agents anymore. The therapy had really run the course of what conventional treatments (could offer). And in that patient population there was about a 40%, what looks like long term cure rate for that patient population, so really fabulous results in large cell lymphoma.

And so, in this trial, this trial ZUMA-2, we're hoping to see similar activity in patients with, again, very difficult-to-treat mantle cell lymphoma, patients who already had standard of care therapies such as a tyrosine kinase inhibitor, and chemo immunotherapy. And we saw very remarkable results. Two-thirds of patients achieved a complete remission in this study, and the follow up is relatively short, but in a subgroup of patients that have been followed for more than two years on, about 40% of patients remain in remission.

So, this would be the first CAR T-cell product that will be available to patients with mantle cell lymphoma?

Right. This would be the first CAR T-cell product that's available for mantle cell lymphoma patients. We hope to see FDA approval sometime this summer. It's been submitted to the FDA for approval, and they have certain timelines that the FDA has to make. And based on that, we know that we should hear the latest by August on whether this drug will be approved.

Is there anything else that people should know about this particular study?

I think the other thing to know is when anybody is looking at any kind of therapy, is what are the risks and benefits of this? It sounds wonderful, augmenting the immune system and you're harnessing the immune system to fight the cancer, which is really what this is doing. But it does have side effects. And, and those side effects are sometimes scary.

There's something called cytokine release syndrome, where basically as I explain it to patients, it's like someone's getting the worst flu of their life. I mean, sometimes they can have fevers as high as 104 (degrees). But when you think about it, that's kind of what we're wanting. We want the immune system to be turned on. We want it to go after this lymphoma, what it thinks is foreign. (But) then we've learned better ways of decreasing those side effects now by using other medications to decrease the incidence and severity of cytokine release syndrome.

The other toxicity is called neurological toxicity, or neurotoxicity, and this can be very disturbing to patients and their family members. Because it can sometimes range from just being a little bit sleepy to people being in a full coma. Luckily, nobody died in this study from this, and we're getting better at intervening earlier to decrease the severity of neurologic toxicity. And so, for the vast majority of patients, it's reversible, but it's definitely something for patients who are considering this (drug) to talk to their doctor about.

Read more here:
CAR T-Cell Therapy a 'Really Exciting' Development in Treatment of Lymphomas - Curetoday.com

Meet this Newcastle University scientist who donated all her royalty money to improve cancer research in India – EdexLive

The danger of cancer continues to cast a shadow of fear in the lives of Indian women. According to experts, the women being diagnosed grow younger by day compared to the same in developed countries. UK-born Dr Asima Mukhopadhyay is a clinician-scientist in womens cancer. Having set up the Project Ovarian Transnational Group of Studies in Kolkata in 2015 and the Kolkata Gynecological Oncology Trials and Translational Research Group, the first-ever research group from India to become a member of the Gynecological Cancer Intergroup, she is one of the leading voices in women's cancer research and in the country. This year, she donated her royalty money as a co-developer of the PARP inhibitor Rucaparib (an anti-cancer drug) to build research capacity for cancer in India. We spoke to her about what needs to be done in cancer research in the country and how we can ensure that treatment reaches the people who need it the most. Excerpts:

What is the current status of women's cancer care in India? Could you outline the areas where we need to move ahead?

The keys areas where we need to move ahead are public awareness through media and community-based programmes. School and college health education would be a major step in ensuring that women with symptoms get to see a cancer specialist in regional cancer centres in the first place rather than reaching thereafter a significant financial drain and loss in valuable time or inadequate treatment. Secondly, we need more trained specialists and dedicated organ-specific cancer teams capable of addressing our specific needs. We also need preventive measures like vaccination, screening, genetic testing and risk-reducing surgeries, as well as ensuring access to life-saving cancer drugs and treatment options.

What led you to make the decision to donate your royalty payment?

On a personal front, I decided on a career in cancer care and research after the demise of my father at a relatively young age in 1998 due to cancer. It was not so long after that I had graduated from Medical College Kolkata. As a cancer survivor family and a young budding doctor, I had the first-hand experience of the emotional, social and economic turmoil and helplessness that one has to undergo to fight this disease and the need for better treatment options and research towards this.

After my return to India in 2015 from the UK, I had joineda reputed cancer centre in Kolkata as an onco-surgeon; I noticed that in India, a majority of cancer patients are not aware of the need to participate in studies or clinical trials which automatically improves the quality of care. In countries like the UK, major cancer research organisations are heavily supported through public funding and donations. We need similar support mechanisms in India including media support and goodwill for promoting better patient care.

Could you describe your discovery around epithelial ovarian cancer and the implications it has for treating cancer?

It had been previously shown by the Newcastle University group of researchers in the UK and various other groups that cancers harbouring a genetic defect in the BRCA genes are very sensitive to a new class of anti-cancer drug called PARP inhibitors. I joined this group in 2008 as a clinician-researcher for my PhD. In 2010, I showed that approximately that 50% epithelial ovarian cancer patients harbour a defect called BRCAness or homologous recombination deficiency (HRD), therefore providing the scope for extending the use for PARP inhibitors to a lot more women compared to only 10-20% of women who have inherited detects in the BRCA gene.

In 2011, this was published as the first-ever report showing the importance of functional BRCAness. I developed a functional biomarker assay (used to understand the mechanism of action of a drug) using ascitic fluid from ovarian cancer patients at the Northern Gynaecological Oncology Centre in Gateshead. After 10 years of my original publication, there is a renewed interest in adopting the functional HRD assay as a better biomarker for selecting patients suitable for PARP inhibitor therapy.

Are women in India at a position where they can seek medical help successfully? How do we spread more gynaecological awareness among the general public?

Partially, yes. There are health systems available and women can seek proper medical health at the tertiary centres. However, many primary and secondary health centres are not much developed and we often find patients referred to us with partial or incomplete treatment. The need of the hour is to train the trainer. Healthcare workers should be trained regarding various cancers, their symptoms, risk factors, hereditary factors and their preventive and treatment opportunities, so that they are able to identify the population at risk of cancers and create health education camps for enlightening the population.

School health awareness campaigns can be created so that children of ages 12 years and above are educated regarding breast self-examination, menstrual hygiene, personal hygiene, obesity and hereditary cancer history so that they are aware of their physical and hereditary risks and act accordingly to prevent cancers in future. These children are the future of our society and if we can incorporate the knowledge of health awareness, the cancer risk in women will sufficiently decrease in future. I firmly believe that if we can incorporate such community-based awareness and screening camps integrated within the existing governmental structures, the access of women from low-income households will surely increase.

See more here:
Meet this Newcastle University scientist who donated all her royalty money to improve cancer research in India - EdexLive

Protagonist Therapeutics, Inc. Common Stock (PTGX) Q1 2020 Earnings Call Transcript – The Motley Fool

Image source: The Motley Fool.

Protagonist Therapeutics, Inc. Common Stock(NASDAQ:PTGX)Q12020 Earnings CallMay 07, 2020, 5:00 p.m. ET

Operator

Good day, and welcome to the Protagonist Therapeutics PTG-300 development update Call. Please note that today's conference is being recorded. At this time, I would like to introduce Don Kalkofen, Protagonist's chief financial officer. Please go ahead.

Don Kalkofen -- Chief Financial Officer

Thank you, operator. Good afternoon, everyone. Please note that a replay of today's call will be available at the Investors section of our website at protagonist-inc.com. Before we begin, I'd like to remind you that today's discussion will include statements about the company's future expectations, plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our quarterly and annual reports on forms 10-Q and 10-K, which are on file with the SEC. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our view should change. With that, I will now turn the call over to Dinesh Patel, president and CEO, to provide you an update on the company's progress to date.

Dinesh Patel -- President and Chief Executive Officer

Thanks, Don. Good afternoon, everyone, and thank you all for joining us today. On today's call, we'll also hear from Samuel Saks, our chief medical officer; and Dr. Ronald Hoffman, Professor of Medicine in Hematology and Medical Oncology at the Mount Sinai Hospital in New York City.

Dr. Hoffman has been involved in the Phase II clinical study of PTG-300 in polycythemia vera, and he will provide a brief overview of the disease and his perspectives on PTG-300 and its potential benefits as the novel treatment for polycythemia vera or PV. Also present for the call today are David Liu, our chief scientific officer and head of R&D and Suneel Gupta, our chief development officer. We are pleased to have all these individuals available to address questions during the Q&A session of today's call.

So let's start with Slide No. 3. As you are well aware, Protagonist started the year 2020 with three clinical assets, all of which have been discovered through the use of our peptide technology platform in six different clinical proof-of-concept studies. The three assets fall in two broad categories: PTG-300 for various blood disorders, most of which are rare disease; and oral GI-restricted targeted peptide PTG-200 and PN-943 for inflammatory bowel disease, or IBD.

All of these assets have a multibillion-dollar potential in multiple indications. PTG-300 peptide mimetic of the natural hormone hepcidin that serves as a master regulator of iron homeostasis storage and distribution in the body was being pursued in Phase II open-label proof-of-concept studies in beta-thalassemia, or beta-thal; polycythemia vera, or PV; hereditary hemochromatosis, or HH; and an investigator-sponsored study in myelodysplastic syndrome, or MDS. As you may recall, a major objective for 2020 was to pick our first clinical indication for PTG-300 that we can progress toward a pivotal study in 2021. Today, we are pleased to announce initial but yet very robust clinical data from our polycythemia vera program.

And the selection and prioritization of polycythemia vera as the first indication for a pivotal study with 300. This decision is based on three criteria: strength and consistency of the clinical data, favorable regulatory path forward and the commercial opportunity. This is our major announcement today. And while most of our discussion will be around 300 and polycythemia vera, let me also take this opportunity to talk briefly about our oral gut-restricted IBD assets, largely in the context of corporate update and cash runway.

The enrollment rate of Phase II studies of these agents, namely the oral alpha-4-beta-7 integrin antagonist PN-943 for ulcerative colitis and the oral interleukin-23 receptor antagonist PTG-200 for Crohn's disease are understandably going to be influenced by the current COVID-19 situation. Therefore, while these studies are continuing, we believe it is appropriate to remove future guidance on the timelines for top line data from these studies. In addition to the decision to focus our efforts toward rapidly advancing 300 in polycythemia vera indication, we are continuing the ongoing proof-of-concept study of 300 in hereditary hemochromatosis as a potential second indication and are also deciding to now discontinue further development of 300 for beta-thalassemia as well as for myelodysplastic syndrome. On the financial side, we ended the first quarter of this year with about $117 million in cash and investments.

By factoring in the delay in enrollment and the associated clinical development costs, coupled with a reduction in operational needs and expenditures, we are now extending our cash runway by an additional six months through the middle of 2022. Now let's go to Slide No. 4, and let me turn to PTG-300, a major highlight of today's call and to provide rationale for why we are pursuing polycythemia vera as our first indication. First and foremost, it's the robust and consistent clinical responses we have seen in our ongoing Phase II PV trial.

Although small, the data set is very compelling and consistent. On six out of six, dose compliant patients treated for up to 28 weeks with 300 are phlebotomy free as of today. These are very noteworthy results. Keeping in mind that prior to entering our study, these subjects were receiving frequent phlebotomies in the weeks leading up to enrollment.

We are obviously very encouraged by these results, and the enrollment in the study continues with eight patients enrolled to date. And we have also decided to now expand the current study from 30 patients to 50 patients. The second factor is the regulatory path forward for the development of 300 in polycythemia vera indication. As you know, approved drugs for polycythemia vera fall into the orphan drug designation category by virtue of it being a rare disease in the U.S.

and Europe. And orphan status provide certain benefits to the drug developer, including seven years of market exclusivity upon FDA approval, prescription drug use of fee waivers and tax credits for qualified clinical trial. The third factor besides the data and the regulatory path is the very significant commercial opportunity that lies ahead of us based on the significant unmet need that exists today for these patients. And specifically, by virtue of PTG-300 being a novel mechanism-based, first-in-class non-cytoreductive natural hormone mimetic agent.

While PV is a rare disease, there are approximately 100,000 people in the U.S. living with this disease, and this number is unfortunately expected to grow as the population ages. The majority of PV patients are treated with phlebotomies, cytoreductive therapies or a combination of those treatments. Jakafi is the only FDA-approved cytoreductive therapy in PV and despite having a limited indication in patients who have had an inadequate response to current treatment, Jakafi is expected to reach almost $2 billion in sales in 2020, and the largest percentage growth is in the PV population, 19% year-over-year based on their most recently quarterly update.

PTG-300 has the potential to address a significant unmet need in this category where there is a lack of new cytoreductive agents in development. 300 offers the potential of keeping patients phlebotomy-free without causing iron deficiency. So to summarize, we are incredibly encouraged by our preliminary but strong and consistent data and, therefore, are electing to focus our resources on expedited development of 300 for polycythemia vera. To speak more about this, I would now like to introduce our chief medical officer, Dr.

Samuel Saks. Sam?

Sam Saks -- Chief Medical Officer

Thanks, Dinesh. As Dinesh mentioned, we are really encouraged by the results we have seen in the ongoing Phase II study of PTG-300 in patients with polycythemia vera. Dr. Hoffman is going to walk you through the study results in detail, but I wanted to highlight why I believe this data has prompted us to focus on PV as the first indication for 300.

The majority of PV patients today are treated with phlebotomy, or phlebotomy in combination with cytoreductive therapies to control erythrocytosis and keep the hematocrit levels below 45%, as indicated in many treatment guidelines. There is a large body of evidence that shows that managing hematocrit is challenging and regardless of best available therapy, they're a substantial portion of patient segments that have poorly controlled hematocrit and therefore, a higher mortality rate compared to age match controls. The treatment paradigm of PV allows patients to enter what I call the danger zone before they get the next treatment. So even those people who are considered well-controlled have increased hematocrit leading up to their phlebotomy.

Self-administered 300 may reduce doctor visits and the anxiety associated with the uncertainty of phlebotomy at that time. Phlebotomy is those of donated blood know, is associated with acute symptoms and difficulties. But the real problem in these patients is the potential for chronic symptoms related to iron deficiency in phlebotomized patients. PTG-300 offers the possibility of putting the control of the hematocrit in the patient's hands with a weekly self-injected mimetic of an endogenous hormone mimetic.

With a clear decision to focus PTG-300 development in PV, we are expanding the current study to include additional patients, and we'll be also hosting a scientific planning meeting with leaders in the field of myeloproliferative neoplasms. We will also be working with patient advocates to discuss pivotal and future studies in polycythemia vera. I will close by saying that while further follow-up and data from additional patients will be needed to confirm the continuity of the robust clinical responses observed to date, we believe this study provides a compelling rationale to initiate planning for a pivotal program in PV. In the near term, we are expanding the current study to include additional patients as we focus on these encouraging results.

Finally, I want to express how proud I am of the entire clinical development team of Protagonist and all the Protagonist employees that helped us to get where we are today with this program. With that, I would like to turn it over to Dr. Hoffman, who needs no introduction. He's a recognized expert in the field of myeloproliferative disorders and is Director of the Myeloproliferative Disease Program at The Icahn School of Medicine at Mount Sinai and an investigator in the 300 study.

Dr. Hoffman?

Ronald Hoffman -- M.D., Director of the Myeloproliferative Diseases Program

Yes. Thank you very much, Sam. Thanks for the opportunity to present this really exciting data. So if we can go to Slide 7, I can educate the audience on what polycythemia vera is so they can have a better understanding of the potential for 300 and put this in context.

So as you can see here, this slide is entitled "What is Polycythemia Vera?" Well, polycythemia vera is a member of a group of chronic hematologic malignancies termed myeloproliferative neoplasms. And these neoplasms are unusual in that patients frequently live several decades. And these neoplasms occur at the level of the hematopoietic stem cell. And unlike leukemia, they are characterized by increased production of mature blood cells.

In polycythemia vera, the cell that's most destructive to the patients are really the increased production of red blood cells. And that's the term erythrocytosis that you've heard previously and we'll hear subsequently. Now the interesting thing about this disease is that there are 100,000 cases of polycythemia vera in the United States. This disease occurs across races and age groups.

And the critical diagnostic warning sign is that of an elevated hematocrit, which is the hallmark of the disease. I think the importance of this drug is that although there's 100,000 cases of these patients, these patients, as I mentioned, live for several decades, so the usage of this drug would be quite prolonged over that period of time. The disease occurs primarily in individuals who are 50 to 70 years of age. There is, however, a higher incidence in young females who present with life-threatening thrombotic events.

The thrombotic events that occur in patients with polycythemia vera include strokes, as well as life-threatening thrombosis of arteries or veins within the venus within the abdominal cavity. There's a very high incidence of acute myocardial infarction, cerebral vascular incidents and strokes. The women that we've talked about, the young women, they are particularly prone to develop thrombosis within the abdominal cavity, especially the hepatic vein, and that leads to a life-threatening condition called Budd-Chiari syndrome. In its most severe forms, it requires liver transplantation.

Over the last 15 years, there's been tremendous understanding, new understanding of this group of myeloproliferative neoplasms. And they've been shown to be characterized by mutations in genes that are associated with myeloid blood cell production. So the myeloproliferative neoplasms are associated with three driver mutations: one involving JAK2, the other gene called calreticulin and the other MPL, which is a receptor for the hormone thrombopoietin. Virtually 99% of patients with polycythemia vera have a mutation in JAK2.

Most commonly, it is a mutation that occurs at exon 14, which is the JAK2V617F mutation. A smaller group of patients have a mutation in exon 12, and those are referred to as exon 12 patients, and they have a similar phenotype, again, elevated hematocrits, increased thrombosis and shorter lifespan due to these thrombotic events and severe erythrocytosis. Next slide, please. We're going to talk now about the diagnosis, symptoms and treatment of polycythemia vera, so that you can get an understanding of the role, the potential role of PTG-300.

The diagnosis of polycythemia vera is triggered by finding an elevated hematocrit serendipitously or by a thrombotic event, and that initiates the physician looking for the diagnosis. So for instance, a patient could present within an acute myocardial infarction and be found to have hematocrit. These warning signs, then prompt, the blood tests to be performed that look for the presence of the JAK2V617F mutation or the exon 12 mutation of JAK2V617F is not present. And sometimes, a bone marrow examination is required to perform histopathologic confirmation of the diagnosis.

This disease is not only complicated by thrombotic episodes, but it's also complicated by burdensome systemic symptoms, including fatigue, headache, visual symptoms, night sweats and itchiness. And this itchiness characteristically occurs on exposure to water and has termed aquagenic pruritus. This might seem like a trivial symptom but aquagenic pruritus can be so severe that patients are unable to shower for months or can lead to such stress that occasionally, we've unfortunately had patients who have succumbed to suicide. Thrombotic events is the greatest risk to patients with polycythemia vera.

These thrombotic events, as I mentioned, include heart attacks, strokes, deep vein thrombosis or pulmonary embolism or the Budd-Chiari syndrome. The cardinal feature of treatment and reduction of this thrombotic risk is to reduce the hematocrit below 45%. Again, the hematocrit is just the measure that we use of the number of red blood cells and the degree of erythrocytosis. And that assures that essentially the viscosity of the blood or the stickiness of the book is reduced, thereby reducing the incidence of thrombosis.

So normalization of the hematocrit using therapeutic phlebotomy is very common, and it is really the first treatment in newly diagnosed patients with polycythemia vera. Unfortunately, therapeutic phlebotomy leads to the removal of red blood cells, which contain iron and it leads to more severe iron deficiency contributing to many of the exacerbation, of many of the systemic symptoms that I referred to previously. And those patients that require frequent phlebotomies or at their advanced stage that is over 60 years of age or have thrombosis, a prior thrombosis, it is the recommendation of the standard of care that those patients all be treated with hydroxyurea, interferon or Jakafi. It is in this situation that 300 is especially attractive drug because it can be used to treat patients who are not requiring myelosuppressive agents or it could be a replacement for those myelosuppressive agents.

Again, the site of the reductive agents are hydroxy and interferon, which are used in combination with phlebotomy, with supplemental phlebotomy, or an alternative drug is Jakafi or ruxolitinib, which is the only U.S. FDA-approved product for phlebotomy. Each of these drugs, and I can go into that in detail during the question-and-answer period are associated with significant adverse effects and have a questionable surrounding their tolerability. Significant evidence, as I've mentioned, shows that controlling the hematocrit below 45% is the most important factor in minimizing thrombosis, cardiovascular events and death due to thrombosis.

Please let's go to the next slide. So we're going to talk a little bit about phlebotomy, which many of you have probably experienced when you donate blood. So most patients receive phlebotomy initially. Phlebotomy is basically the removal of a unit of blood to reduce the hematocrit below 45%.

So our target is to keep those patients always below 45% because it's been well demonstrated in the literature that, that reduces significantly the incidence of thrombosis. And the incidence of thrombosis has been shown to be reduced when the degree of time with an adequate of 45% is maximized. In addition, these would patients receive low-dose aspirin to paralyze their platelets and their or further augment this antithrombogenesis in patients with polycythemia vera. Patients who undergo phlebotomies will often report feeling tired or dizzy after the phlebotomy.

And especially in the elderly, this is a major factor. Many of these patients become hypertensive, require long stays in our outpatient facility or require fluid infusions because or going to congestive heart failure because of their poor fluid balance. Furthermore, regular phlebotomy results in iron deficiency that makes the augmentation of iron deficiency that may have debilitating symptoms. As I mentioned, particularly severe fatigue, weakness and cognitive impairments.

This cognitive impairment is a really big deal because many of the patients complain of having a fuzzy brain syndrome, and they cannot concentrate and do their jobs. In addition, some of the patients have craving for unusual substances such as ice or clay, which is termed pica. And then, unfortunately, some of the patients have a restless leg syndrome, which prevents them from going to sleep. Three or more phlebotomies in a year in those patients receiving hydroxyurea is associated with an inferior prognosis and a higher incidence of thrombotic events.

So you can also think that in that situation, even in a patient who is receiving hydroxyurea, their combination therapy with 300 could eliminate those frequent phlebotomies and further improve the treatment regimen for these patients. I think the most important part that you'll see about this drug are the real high-quality aspect of it is that we see these patients, let's say, a three or four-month intervals. At that three or four-month interval, we see that they have an elevated amount of hematocrit and that triggers us to do a phlebotomy. But in reality, we have no way to monitor them during the interval between their visits, and it's likely that for significant periods of time, they have an elevated hematocrit that's only detected at the time of their visit to our clinic.

So as you'll see, the really cool part about PTG-300 is that there's a sustained hematocrit control, which we've really never been able to achieve with any of the other agents or with phlebotomy alone. Let's go now on to Slide No. 10, which is PTG-300 and non-cytoreductive hepcidin hormone mimetic, its mechanism of action. So how does this drug really work? Well, hepcidin hormone, has been established recently in the last couple of decades, is playing a primary role in promoting the sequestration of iron and macrophages and decreasing iron availability for the production of red blood cells.

So macrophages are a type of white blood cell, and they are present not only in the bone marrow, but they're also present in all other body tissues. But the macrophages in the marrow are termed nursing cells because their activity is essentially to feed iron to red blood cells in the marrow and to alter to allow them to produce additional red cells. This process is disregulated by the JAK2 mutation leading to erythrocytosis. So PTG-300 is believed to limit the excess production red cells in polycythemia vera by essentially allowing that iron to remain in the macrophages.

Therefore, preventing its transfer into the erythroid precursors. In addition, it blocks the iron that's present in the macrophages in the tissues outside of the marrow. And therefore, we believe alleviates many of the systemic symptoms that are associated with polycythemia vera. Let's now go on to Slide 11, which is the Phase II study design.

This is a really interesting manner in which this study has been constructed. You can see there are three phases. Part one is the dose-finding period, which is over 28 days. And there are two components to that.

I believe effective dose-finding phase, where we essentially dose-escalate patients to meet the inadequate requirements. Then a 12 to 14-week period where we essentially have efficacy evaluation that is to maintain the patient's hematocrit below 45%. And then there's part two as a blinded withdrawal where the patients are randomized to receive either the fixed active dose or placebo dose for up to 12 weeks. And then I'm sure the patients will be happy about that, those that go on placebo, they will then allow them we will be allowed to put them on to an open-label extension phase up to 52 weeks where they will again be able to receive 300.

If the patient's hematocrits exceed 45%, they get supplemental phlebotomies. Let's go on to Slide No. 12. This is essentially the responses that we've seen in the seven patients that have been described, that have been evaluated.

The red triangles indicate the phlebotomies, and you can see a lot of them to the left of the solid line. And that's the 32 weeks prior to treatment. And you can see that each of these patients, and these were entry criteria, had at least three phlebotomies during that period. And then you can see this dotted line, and that's the time at which the doses the drug was started.

And the first thing that strikes you is that there are a lot of red triangles to the left and only one red triangle to the right, and that's one of our patients who missed one dose due to the unfortunately, due to the pandemic. And the numbers indicate the doses that were administered over that period of time. So for instance, you can see in patient 150201, there was a dose escalation and then de-escalation, which I'll discuss on the subsequent slide. So this slide really summarizes and probably is our most important slide.

And it basically shows that with the administration of this drug and careful titration that phlebotomy is almost virtually eliminated. Next slide. Let's focus on two patients. One is the top patient, which is the blue line.

And you can see that this patient, this is the individual who missed the dose because of the COVID infection. And you can see that he was started at 10 milligrams, then went up to 20 milligrams. And on 20 milligrams, he had a hematocrit 47.5, he was unable to come in at that time because of the COVID infection. So we increased his dose to 40 milligrams, his hematocrit dropped, but it was still above 45.

He came in, we phlebotomized him, and we've kept him now on 40 milligrams, and you would have seen on Wednesday, and he did not require a phlebotomy and his hematocrit was below 45. If you look at the bottom patient who is in bright red, you can see that, that patient started at time 0 on 10, then was increased to 20 and then on week seven got 40 milligrams and then on week 12 got 80 milligrams. And you can see that, that led to a hematocrit dropping to 37.5. We cut our dose to 40 milligrams, and you can see that over that period of time, she has remained phlebotomy-free.

We saw her on Wednesday, and she again remains below hematocrit of 45. So there's a dose adjustment that you can easily do. The drugs are being administered at home by the patients, giving them a lot of freedom and also empowering them to control their own disease. If we go to Slide 14.

This addresses how do we know that PTG-300 is really hitting its target. And what we're measuring here is serum ferritin. And if you can recall, ferritin is a molecule that reflects storage iron. And you can see these numbers in the vertical column, and if you're below 25, that indicates that one is iron-deficient.

And you can see it with the administration of the drug at subsequent doses over time, the ferritin doses, the ferritin levels increased in each of these patients except the bottom line where a patient received an extremely hematocrit control with an extremely low dose of 300. So these data indicate that the drug is acting on target. What about the adverse defense? Because this is a chronic disease, one must anticipate that patients will be treated over decades. This is a small sample set but you can see that we had no serious adverse events and the adverse events that were recorded were essentially just irritations, essentially at the injection site that slowly resolved and one of the patients had a bruise at a 10-milligram dose.

Let's go on now to Page 16, which is our summary. So just to start this off. I think phlebotomy has probably been used for almost 100 years. And for at least, since I've been in this field, which is from the 70s, there's been great debate about what is the optimal myelosuppressive agent.

There's great concern about chemotherapy being used in these patients, perhaps increasing the incidence of evolution to acute myeloid leukemia. We never really anticipated that a hormone therapy might be used for this type of disease. So I think this trial really represents a paradigm shift and it has great importance for patients with polycythemia vera. So I think we can easily conclude that the additional data demonstrates the potential of this drug to almost entirely avoid the need for bottoming the treatment of polycythemia vera.

All dose compliant patients were phlebotomy-free. Persistent control of hematocrit levels, I think that's really one of the most important issues is that the patients have a sustained control of their hematocrit, which we anticipate will lead to sustained alleviation of their systemic symptoms and elimination of thrombotic episodes. And again, as I tried to indicate to you these elevated hematocrit levels are associated with significant cardiovascular events such as heart attack and stroke. This drug also offers the possibility of weekly administration without the up and down excursions inherent in phlebotomy therapy or any of the toxicities associated with phlebotomy therapy that I discussed with you.

Also, this reduction in phlebotomy may allow sufficient iron to be available systemically to avoid symptoms that we know that are related to iron deficiency. So PTG-300 has the potential as the first non-cytoreductive therapy for PV. This drug is well tolerated and has a safety profile similar with results in prior studies. So as you can see from my presentation, I'm extremely enthusiastic about this drug and its future.

Thank you for your time.

Dinesh Patel -- President and Chief Executive Officer

Thank you, Dr. Hoffman. I would like to note that the results we have discussed today address the study data as of May 1, and the study continues to enroll. And our plan will be to submit to present additional data at upcoming medical meetings.

So at Protagonist, we are now working on four clinical programs with our three candidates, all discovered through our technology platform. Our priorities are: one, advancing PTG-300 in polycythemia vera as well as in hereditary hemochromatosis; two, advancing PN-943 to a Phase II study in ulcerative colitis; and three, working closely with our partner, Janssen, to continue Phase II development of PTG-200 in Crohn's disease. As a result of our ability to limit our focus with 300 to PV and HH, we have organized our efforts to extend our cash runway for an additional six months. We have taken steps to manage and lower our operating costs and align our resources around our current studies.

As a consequence, we now have adequate financial resources to fund planned operating and capital expenditures through the middle of 2022. Finally, we are mindful of the impact that the current coronavirus outbreak may have on our local operations and global activities. As we disclosed in our financial results released today, we are suspending guidance for PN-943 Phase II initiation and PTG-200 Phase II data, and we are actively working to minimize impact on timelines and move as quickly as conditions would permit. Our priority is maintaining the health and safety of our employees and those who are participating in our studies.

We will continue to monitor changing conditions carefully and provide updates as appropriate. With that, we would like to now open up the call for questions. Operator?

Operator

[Operator instructions] Our first question comes from the line of Chris from Nomura. Your line is now open.

Chris Marai -- Nomura Instinet -- Analyst

Hi. This is Chris Marai from Nomura Instinet. Maybe the first one is for the physician on the line. Thank you so much for the overview of PV.

I was curious how you look at a therapeutic like PTG-300 in terms of clinical practice on sort of an everyday basis as you see PV patients? And how do you think it may fit, assuming this profile remains consistent in sort of the treatment lines of PV, how you may see its usage, in particular relative to drugs like Jakafi? Thank you.

Ronald Hoffman -- M.D., Director of the Myeloproliferative Diseases Program

OK. I think that's a really terrific question. I think its use would be quite wide. I think virtually all patients with PV would be candidates for this drug.

As you can see, we have treated young patients and also older patients with this drug. So it's been well tolerated. I think the advantage, again, is that, especially with young patients, those individuals, we do not want to give life-long myelosuppressive therapy or interferon or Jakafi because of unanticipated potential for unanticipated adverse effects. So if they have an increased phlebotomy requirement, this would be an ideal treatment for those folks because basically, it would free them up from returning to the clinic as frequently as they do and requiring repeated phlebotomies.

When we risk-stratify these patients, those patients that go on the three treatments that I've discussed before, frequently, they still require phlebotomies, and it's been shown by European investigators, if you have additional phlebotomies during your administration of these drugs, that you are an increased risk of thrombosis. So in that setting, this drug could be an adjunctive agent that would eliminate the needs for phlebotomy. Alternatively, and I could see this developing quite quickly, patients are frequently unwilling to take any of these agents, especially hydroxyurea and interferon because of the potential of hydroxyurea and the concern about interferon essentially having systemic symptoms, problems with individuals about immune disease and also its effect to exacerbate depression in patients. So in those individuals, I could see and even in those high-risk patients, if we can control their hematocrits with this drug, which I think we can easily do, and we've demonstrated that.

That this drug would be a real competitor for any of those agents. So I think it could be essentially utilized potentially for the broad swath of patients with polycythemia vera. So I think and for long periods of time, that's the issue that I'd like to really emphasize to you. For instance, like young females who have Budd-Chiari syndrome, and we usually put those young females on myelosuppressive therapy and interferon for life-long periods of time, and they can live several decades.

They would far prefer being on a non-chemotherapy, non-biologic agent like interferon, it would really liberate them, especially from the adverse effects.

Chris Marai -- Nomura Instinet -- Analyst

OK. That's very helpful. And then I was wondering if we could touch upon the data for a minute. Dr.

Hoffman, could you elaborate on some of the effects of spleen size that you may have observed in the trial, if any? What you would hope to see there on an endpoint like that in a patient population like this? Thank you.

Ronald Hoffman -- M.D., Director of the Myeloproliferative Diseases Program

Yes. So in this situation, what you have to understand is this is not myelofibrosis. So in reality, most patients with or virtually all patients, I'll say most, the overwhelming majority of patients with patients with polycythemia that don't have symptomatic splenomegaly. So the endpoints that have been used in the past, let's say, for Jakafi for reduction of spleen size are of minimal importance.

So these patients, even though some of them have high-risk disease, really didn't have they had minimal splenomegaly at all, only 40% of patients with polycythemia vera have splenomegaly and only for our advanced disease it's symptomatic. So the sample size is too small. In animal models, when hepcidin mimetics were given, those are polycythemia vera animal models, the administration of a different hepcidin mimetic did lead to reduction in splenomegaly but we really were not able to assess this because none of these patients really had significant splenomegaly. So we await treating patients like that to see if the data in the mice is recapitulated in humans as it relates to spleen size.

Chris Marai -- Nomura Instinet -- Analyst

Very helpful. Thank you.

Operator

Our next question comes from the line of George Farmer of BMO. Your line is now open.

Gobind Singh -- BMO Capital Markets -- Analyst

Hi, everyone. This is Gobind Singh on for George. Congrats on making a decision and moving forward with those two indications. I guess we had two buckets of questions.

The first two, maybe for Dinesh. I know you guys were thinking about once-weekly dosing and possibly twice weekly dosing in beta-thal. I was wondering if maybe going forward, at least with PV, do you think you might be looking at twice weekly dosing at all? And I was wondering since we are moving past beta-thal and MDS, if you'd be willing to comment at all as to what kind of data we're seeing in those indications? And I'll have a follow-up for Dr. Hoffman, if that's OK.

Dinesh Patel -- President and Chief Executive Officer

Yes. Gobind, thanks for the question. And I will have Sam Saks, our CMO, answer the first question.

Sam Saks -- Chief Medical Officer

Sure. So with respect to the use of 300, we think that it's going to be used widely. You were asking me...

Dinesh Patel -- President and Chief Executive Officer

About the once-weekly.

See the rest here:
Protagonist Therapeutics, Inc. Common Stock (PTGX) Q1 2020 Earnings Call Transcript - The Motley Fool

Chemotherapy for Certain Small, Hormone-Receptor-Positive, HER2-Positive Breast Cancers Seems to Improve Survival – Breastcancer.org

When looking at treatment outcomes for small, hormone-receptor-positive, HER2-positive breast cancers that have not spread to the lymph nodes, a study suggests that women diagnosed with cancers 810 mm (about 0.31 inches to 0.39 inches) in size had better survival when they were treated with chemotherapy after surgery compared to women diagnosed with smaller cancers.

The research was published on April 9, 2020, by the journal JAMA Network Open. Read the abstract of Association of Survival With Chemoendocrine Therapy in Women With Small, Hormone Receptor-Positive, ERBB2-Positive, Node-Negative Breast Cancer.

The HER2 gene is also called the ERBB2 (Erb-B2 receptor tyrosine kinase 2) gene.

Research shows that very small, node-negative, hormone-receptor-positive, HER2-positive breast cancers have a 5-year recurrence risk the risk of the cancer coming back within 5 years that ranges from 5% to 25%, with or without treatments after surgery. Doctors call treatments given after surgery adjuvant treatments.

Because HER2-positive cancer is considered more aggressive than HER2-negative breast cancer, it is usually treated with chemotherapy after surgery to reduce recurrence risk. Still, it has been unclear whether the benefits of treating very small, node-negative, hormone-receptor-positive, HER2-positive breast cancers with chemotherapy after surgery outweighed the risks.

It wasnt clear what to do with these patients, who make up a really small population of breast cancer patients, Anurag Singh, M.D., of Roswell Park Comprehensive Cancer Center, one of the researchers who did the study, said in an interview.

We know that if you have an ERBB2 tumor, it's worse, and the idea has been they should get chemotherapy,he continued. You have an otherwise healthy 60-year-old, mammographically screened and detected patient. When you give them the information, they're saying, 'OK, I have all of these good things, but I've got a 2-mm tumor and you want to give me 6 months of chemo. Are you serious? I'm going to lose my hair, I'm going to have this, I'm going to have that. It seems like an awful long way to go.' We didn't really have good evidence for them.

The researchers looked at the records of 10,065 women diagnosed with node-negative, hormone-receptor-positive, HER2-positive breast cancer that was 10 mm or smaller in size between 2010 and 2015.

All of the women were treated with hormonal therapy after surgery:

From 2013 to 2015, anti-HER2 therapy such as Herceptin (chemical name: trastuzumab) was coded differently than chemotherapy in patient records; 15% of the women treated during this time had either chemotherapy or anti-HER2 therapy alone.

Follow-up time ranged from about 2 years to about 5 years.

The researchers compared the outcomes of women treated with hormonal therapy and chemotherapy to women treated with hormonal therapy alone. They also looked to see if the size of the cancer affected any benefits from chemotherapy.

The analysis showed that chemotherapy was associated with better overall survival for women diagnosed with cancers that were 810 mm in size. Women diagnosed with cancers that were smaller did not seem to get any survival benefits from chemotherapy.

To our knowledge, this is the first report to suggest that there is an association between improved survival and adjuvant chemoendocrine therapy specifically for HR-positive, ERBB2-positive tumors 8 mm to 10 mm compared with those smaller than 8 mm, the researchers wrote. It is evident that tumors 10 mm and smaller represent a heterogeneous group whose treatment should be tailored to improve the risk-to-benefit ratio of systemic therapy.

The results of this study offer helpful information about which women may benefit from chemotherapy after surgery for very small, hormone-receptor-positive, HER2-positive breast cancer that hasnt spread to the lymph nodes.

Still, the results are based on extremely small differences in cancer size millimeters and require expert pathology review of the cancer. The researchers also didnt know the exact chemotherapy regimens the women had.

Also, anti-HER2 medicines, such as Herceptin, are often given along with chemotherapy. In this study, for 2 years of the 5-year study, anti-HER2 therapy and chemotherapy were not coded differently. So, a number of women may have been receiving both anti-HER2 therapy and chemotherapy during that time, which may have affected the study results.

If youve been diagnosed with a very small, hormone-receptor-positive, HER2-positive breast cancer that hasnt spread to the lymph nodes and are considering treatments after surgery, it makes sense to talk about this study with your doctor. The results offer more information about outcomes and can help you decide on the best treatments for your unique situation.

For more information on chemotherapy, including types of medicines and side effects, visit the Breastcancer.org Chemotherapy pages.

Written by: Jamie DePolo, senior editor

Published on May 7, 2020 at 12:02 PM

Excerpt from:
Chemotherapy for Certain Small, Hormone-Receptor-Positive, HER2-Positive Breast Cancers Seems to Improve Survival - Breastcancer.org

World Thalassaemia Day: What does the condition mean for pregnancy? – The Indian Express

Updated: May 8, 2020 3:18:58 pm

By Dr Uma Vaidyanathan

Thalassaemia is a disorder of the haemoglobin structure. A tetramer molecule present in the RBCs, haemoglobin is responsible for supplying oxygen in the body and is a rich source of protein in the blood. The human Hb/HbA has two sets of globin chains. These are a-globin chain and -globin chain. Four genes (two inherited from the mother and two from the father) regulate the production of a-globin chain, while only two genes (each inherited from father and mother) control the production of -globin chain.

The thalassaemia syndromes are characterised by a basic defect in the synthesis of one type of globin chains. As a result, there is insufficient Hb content in the resultant red cells, leading to decreased haemoglobin concentration, anaemia and need for multiple blood transfusions in severe cases.

Each year, more than 70,000 babies are born with thalassaemia worldwide and this defect is very often seen in the Indian subcontinent. Haemoglobin electrophoresis is the gold standard in diagnosing this condition. Patients with thalassemia traits do not require long-term monitoring. They usually do not have iron deficiency, so iron supplements are unlikely to improve their anemia.

Read| Pregnant during the COVID-19 crisis? Heres how to take care of mental health

Alpha thalassaemia

In alpha thalassaemia, the hemoglobin does not produce enough alpha protein. To make alpha-globin protein chains we need four genes, two on each chromosome 16. We get two from each parent. If one or more of these genes is missing, it will result in alpha thalassemia. The severity of thalassemia depends on how many genes are faulty, or mutated.

One faulty gene: The patient has no symptoms. A healthy person who has a child with symptoms of thalassemia is a carrier. This type is known as alpha thalassemia minima.

Read| Covid-19 and pregnancy: What expectant mothers need to know

Two faulty genes: The patient has mild anemia. It is known as alpha thalassemia minor.

Three faulty genes: The patient has hemoglobin H disease. This is a type of chronic anemia. In this case, the patient needs regular blood transfusions throughout their life.

Four faulty genes: Alpha thalassaemia major is the most severe form of alpha thalassemia. It is known to cause hydrops fetalis, a serious condition in which fluid accumulates in parts of the fetus body. A fetus with four mutated genes cannot produce normal hemoglobin and is unlikely to survive, even with blood transfusions.

Beta Thalassemia

Two globin genes are required to make beta-globin chains: one gene from each parent. Beta thalassaemia is caused when one or both genes are faulty.

Severity depends on how many genes are mutated.

One faulty gene: This is called beta thalassaemia minor.

Two faulty genes: There may be moderate or severe symptoms. This is known as thalassaemia major (earlier known as Colleys anemia).

Medical management of thalassaemia major depending on severity would be:

Blood transfusions

Chelation therapy removal of excess iron overload in body

Bone marrow transplant

Gene therapy

Management during Pregnancy can be divided as follows:

Periconceptional care

Screening and counseling pre-pregnancy: Screening can identify couples having 25 per cent risk or more of having a pregnancy with signi?cant haemoglobinopathy. If a pregnant woman is found to be a carrier of haemoglobinopathy, the partner needs to be screened as soon as possible. If a risk of the fetus having major haemoglobinopathy is detected, urgent expert counselling is provided to the couple so that they can make an informed choice regarding the prenatal diagnosis and the possible termination of pregnancy.

Folic acid supplementation: Beginning in the preconceptual period, at least three months prior to conception, folic acid in the dosage of 5 mg/day helps in preventing neural tube defects.

Some additional tests also might be needed. Doctor might ask the patient to take blood sugar and thyroid function tests. Patients could be asked for cardiovascular assessment. Ultrasound of liver and the gallbladder (and spleen, if present) should be performed. This helps in detecting gallstones and evidence of liver cirrhosis due to iron overload or transfusion-related viral hepatitis.

Antenatal care

Women with thalassaemia should be reviewed on a monthly basis until 28 weeks of gestation and fortnightly thereafter. Women with thalassaemia are best treated in a multidisciplinary team setting, including an obstetrician with expertise in managing high-risk pregnancies and a hematologist.

Ultrasound scanning

An early scan after 7 to 9 weeks of gestation is needed to determine viability as well as the presence of a multiple pregnancy. A detailed anomaly scan must also be done after 11-12 weeks and 18 to 20 weeks of gestation. Later, ultrasounds may be needed to assess foetal growth restriction.

Care during labour and delivery

Thalassaemia is not an indication for cesarean section. Patients may need blood transfusion in case of excessive blood loss during the delivery.

Postpartum care

Women with thalassemia are at high risk for venous thromboembolism due to the presence of abnormal red blood cells in the circulation.

Breastfeeding is safe and should be encouraged. In addition, there is no contraindication to the use of hormonal methods of contraception, such as the combined oral contraceptive pill, the progestogen-only pill, hormonal implants, and the Mirena intrauterine system in women with thalassaemia.

(The writer is Senior Consultant, Obstetrics and Gynecology Fortis Hospital, Shalimar Bagh.)

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World Thalassaemia Day: What does the condition mean for pregnancy? - The Indian Express

A cystic brosis success story — over 30 years | Health – The Union Leader

In August 1989, scientists made a blockbuster discovery: They pinpointed the faulty gene that causes cystic fibrosis, a cruel lung disease that killed many of its victims before they reached adulthood.

The human genome was uncharted territory, and the gene hunt had become an all-out international race, with laboratories in three countries searching for the root of the disease.

That fall, biologist James Wilson stood before an audience of researchers, physicians and cystic fibrosis patients and their families and described gene therapy, a way to replace the faulty gene with a good copy. Wilson had intended his talk to be technical and prophetic, but he was overwhelmed by the surging thrill in the room that science was about to save peoples lives.

It was one of the most amazing experiences that Ive ever had, Wilson said, adding, The expectations were through the roof.

The importance of the cystic fibrosis gene discovery went far beyond a single illness. It helped build the case for the $3 billion project to sequence the entire human genome, which would alter understanding of human biology and shed light on rare and common diseases.

But the story of cystic fibrosis has been illustrative in a way that no one could have anticipated back then. In the early days of human genetics, the path seemed straightforward: Find the gene, fix the gene and repeat for other diseases. The cystic fibrosis journey, from an exuberant moment of insight to a major success, would take 30 years of persistent, methodical work: a feat of science, business, fundraising and patience that has become a model for other diseases.

I specifically remember sitting with my doctor in the exam room, having the conversation that the gene was discovered, said Josh Taylor, 48, of Virginia Beach, who has cystic fibrosis. And him telling me the cure is just he literally said, In 5 to 10 years, were going to beat this.

It was not until late 2019 that another breakthrough fulfilled many of the hopes of 1989. Now, Taylor has what he has been waiting for all these decades a new drug, Trikafta, that is effective for 90 percent of patients. Doctors marvel at what they think will be possible if it is given at an early age: a full life span.

Cystic fibrosis developed when a child had the bad luck to inherit two faulty genes, one from each parent. Back then, there was no test to detect whether a parent carried a defective gene because no one even knew what the gene was.

As scientists developed new tools to probe human genetics, cystic fibrosis quickly became one of the top targets. It is the most common inherited disease among Caucasians, afflicting 30,000 Americans, and its motivated patient group spurred the work forward with funding.

All these human disease genes were floating around. We knew they were inherited, but we knew very little. We didnt know what the genes were, or where they were located, said Robert Nussbaum, a medical geneticist who was hunting genes for other diseases.

Francis Collins, now director of the National Institutes of Health and then a scientist at the University of Michigan working on cystic fibrosis, was photographed for the universitys graduates magazine sitting in a haystack holding a needle, to convey the magnitude of the technical challenge.

Almost everybody knew some family where it had happened, and it was heartbreaking to see what these kids go through, Collins said.

Robert Beall, then an executive vice president at the Cystic Fibrosis Foundation, which was funding the work, was also the most impatient human being I ever met to his credit, Collins said.

Collins partnered with biologist Lap-Chee Tsui, in Toronto holding joint lab meetings at a midway point on the long drive, in London, Ontario.

After years of work, Tsuis lab had narrowed the search to ever smaller stretches of DNA, pioneering new techniques in the search for the gene. Collins had invented a method to speed up the process called chromosome jumping, which allowed scientists to leap over sections of DNA something he compares to leaping from one street corner to the next to initiate searches. Jack Riordan, another scientist in Toronto, discovered a bit of DNA that looked like it might be a part of the gene, providing an essential lead.

In May, a scientist in Tsuis lab found a tantalizing clue three missing letters of DNA in a patient with cystic fibrosis. The team would need to confirm that this genetic mutation was the cause of the disease. Collins and Tsui were at a scientific conference at New Haven, Conn., a month later when they got more evidence.

One rainy night after the days program was over, the pair raced to Tsuis room, where he had installed a portable fax machine to receive updates from the lab. Among the papers that had spilled onto the floor was a table showing those three letters of DNA missing in multiple patients with cystic fibrosis, while they were present in healthy people.

Lap-Chee was a little more skeptical, Ive got to see more data, Collins recalled. I bought it, that was it. I wanted to scream and jump up and down.

The news report triggered frantic preparations to present the findings officially, and the work was published in Science magazine that September in three papers.

Collins would testify before Congress that it was necessary to fund the human genome project because the flat-out effort to find the cystic fibrosis gene simply would not be scalable in trying to understand thousands of other diseases.

Gene therapy, the thinking went, would soon cure cystic fibrosis, marking a turning point in the treatment of genetic diseases. The idea was relatively straightforward: Use a virus to ferry a good, functioning copy of the gene into patients lung cells.

But human biology turned out to have all sorts of ways of resisting an easy fix, and it quickly became clear that gene therapy would not be simple in real lungs.

Then the entire gene therapy field screeched halted in 1999 with the death of Jesse Gelsinger, a teenager with a metabolic disorder who died after being treated for the disorder in one of Wilsons gene therapy trials.

As the hope for a high-profile gene therapy success crashed, research continued on the basic, less glamorous work to untangle what went wrong with the cystic fibrosis gene. That understanding made it possible to develop ways to screen chemicals, to see if any showed promise as a drug.

Beall and Preston Campbell of the Cystic Fibrosis Foundation visited Aurora Biosciences, a San Diego biotech company that used robotics to massively speed up such testing.

Bob and I were like kids in a candy shop, Campbell recalled. After a small initial investment, the foundation stunned the nonprofit world in 2000 by awarding the company $40 million, a new kind of venture philanthropy arrangement in which if the company was successful, the nonprofit group would receive a share of the royalties.

A Massachusetts company, Vertex Pharmaceuticals, acquired Aurora in 2001, and although the cystic fibrosis work continued, it was considered a long shot, called the fantasy project internally, recalled Fred Van Goor, a scientist who joined the company around that time and became the biology lead for the cystic fibrosis program.

The scientific problem was huge: The most common gene mutation in cystic fibrosis created a protein that couldnt do its essential job in the cell. The protein didnt fold correctly, which interfered with its ability to reach the surface of the cell. And it didnt function well once there, where it was supposed to work as a gate. That meant theyd need multiple drugs to help patients one to get the protein to the right spot, the other one to open the gate.

Vertexs first drug candidate was focused on just one of the problems getting the gate to work better. Alone, it would help only about 4% of patients, whose disease was caused by a rare mutation. That drug, Kalydeco, was approved in 2012, but it remained unclear whether a drug could be made that would work for a larger group of patients.

Then, Vertexs main product a hepatitis C drug was eclipsed by a better treatment from a competitor, and the future of the company and its cystic fibrosis research was cast in doubt.

It obviously created an incredible crisis here at Vertex, said Jeff Leiden, chief executive of the company.

Vertexs board decided to bet on cystic fibrosis, and in 2015, a two-drug combination called Orkambi, was approved for a larger group of cystic fibrosis patients. Excitement about the drugs began to yield to a societal debate about their high prices; Orkambis launch price was $259,000 a year.

Meanwhile, the company would need to develop a third drug to treat more patients.

Drug trials are blinded so that neither the patients nor the scientists know which people are receiving the drug and which are receiving a placebo. When Trikafta, the triple drug combination that would ultimately be approved, was unblinded from one trial in October 2018, researchers finally saw the slide showing how the drug affected lung function.

There was a stunned silence in the room for a full minute. The drug worked.

Ten percent of cystic fibrosis patients, or about 3,000 people in the United States, are still waiting for a therapy that works for them.

Stacy Carmona, who was born just three years before the gene was discovered, is one of them.

Im so excited for the community. Im so excited for the CF friends I have who so desperately need the drug. There are so many people hanging on by a thread, waiting for this, Carmona said. The flip side of that is you cant help but wonder when is it going to be my turn?

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A cystic brosis success story -- over 30 years | Health - The Union Leader

Selecta Biosciences Appoints Dr. Goran Ando to its Board of DirectorsGlobal pharmaceutical and biotech industry veteran brings significant clinical…

WATERTOWN, Mass., April 28, 2020 (GLOBE NEWSWIRE) -- Selecta Biosciences, Inc. (NASDAQ: SELB), a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its immune tolerance platform, ImmTOR, today announced the appointment of Dr. Goran Ando to its Board of Directors, replacing Amir Nashat, effective April 24, 2020. Amir will continue to serve in an advisory capacity to Selecta.

The addition of Dr. Ando to our Board means that Selecta now has another proven leader with a successful track record in product development and commercialization, said Carrie S. Cox, Chairman of the Board, Selecta Biosciences. This addition to our team puts us in a position of strength for the next evolution of ImmTOR initiating the Phase 3 clinical trial of SEL-212, bringing our gene therapy program into the clinic, and applying the platform in other areas of significant unmet need. I would also like to recognize Amir Nashat for his long-term commitment to our organization and the important role he played in advancing Selectas scientific platform. From an early stage, Amir recognized the potential of ImmTOR for patients with serious diseases, and I want to thank him for helping put Selecta in the position it is in today.

The opportunity to work alongside the Selecta team to advance the ImmTOR platform is of undeniable interest to me, said Dr. Ando. The ability to re-dose patients with AAV gene therapy may be pivotal in improving outcomes, while Selectas late-stage asset in chronic refractory gout could provide patients with this debilitating disease a much-needed alternative. I look forward to being part of the effort to increase the applicability of the ImmTOR platform for the benefit of patients.

Dr. Ando brings more than 37 years of experience as a respected global pharmaceutical leader. He currently serves as the Chairman of the Board for Eyepoint Pharma, and holds seats on the Boards of Parexel, Tessa Therapeutics, and EUSA Pharma. He is also the retired Chairman of the Board of Novo Nordisk A/S. Dr. Ando began his pharmaceutical industry career as Medical Director of Pfizer AB, progressing to Director, Clinical Research with Pfizer International in the U.S. He went on to hold various senior positions at leading global healthcare and pharmaceutical businesses, including Bristol-Myers Squibb and GlaxoSmithKline. He was the VP, Medical and Scientific Affairs at Bristol-Myers Squibb before taking the role of President of the Astra Research Centre in Sweden. In 1989, Dr. Ando joined GlaxoSmithKline, where he held various senior appointments, including Research & Development Director for Glaxo Group Research. He later joined Pharmacia AB as Executive Vice President, and ascended to Deputy CEO in 1995, moving to the U.S. in 1997 to lead R&D with additional responsibilities for manufacturing, information technology, business development and M&A. During his eight-year tenure as Head of R&D at Pharmacia/Pharmacia & Upjohn, 17 new drugs were approved by the U.S. Food & Drug Administration prior to Pharmacias acquisition by Pfizer for $60 billion. He then served as the Chief Executive Officer of Cell Tech Group PLC, one of the most successful European biotech companies, until it was acquired by UCB Pharma for $3 billion in 2005. He has been a Senior Adviser to leading specialist healthcare investment group Essex Woodlands since 2007. Dr. Ando received his Bachelor of Arts degree from Uppsala University in Sweden and Doctor of Medicine degree from Linkping University in Sweden.

About Selecta Biosciences, Inc.Selecta Biosciences, Inc. is a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its immune tolerance (ImmTOR) platform. Selecta plans to combine ImmTOR with a range of biologic therapies for rare and serious diseases that require new treatment options due to high immunogenicity. The companys current proprietary pipeline includes ImmTOR-powered therapeutic enzyme and gene therapy product candidates. SEL-212, the companys lead product candidate, is being developed to treat chronic refractory gout patients and resolve their debilitating symptoms, including flares and gouty arthritis. Selectas proprietary gene therapy product candidates are in preclinical development for certain rare inborn errors of metabolism and incorporate ImmTOR with the goal of addressing barriers to repeat administration. Selecta is based in Watertown, Massachusetts. For more information, please visit http://selectabio.com.

Forward-Looking StatementsAny statements in this press release about the future expectations, plans and prospects of Selecta Biosciences, Inc. (the company), including without limitation, statements regarding the progress of the clinical development of SEL-212, expectations surrounding the enrollment and design of the Phase 2 head-to-head (COMPARE) clinical trial comparing SEL-212 and Krystexxa, timing of related data readouts and the ability of the COMPARE results to inform the planned Phase 3 clinical trial of SEL-212, the anticipated timing of the planned Phase 3 clinical trial, whether the head-to-head trial with Krystexxa will demonstrate superiority, the unique proprietary technology platform of the company and the unique proprietary platform of its partners, the potential of ImmTOR to enable re-dosing of AAV gene therapy, the potential of SEL-212 to fulfill unmet needs in chronic refractory gout patients including sustained SUA reduction, reduced flares, and once monthly dosing, the companys commercial plans, the ability of the companys ImmTOR platform, including SEL-212, to unlock the full potential of biologic therapies, the potential of SEL-212 to treat chronic refractory gout patients and resolve their debilitating symptoms, the potential treatment applications for product candidates utilizing the ImmTOR platform in areas such as enzyme therapy and gene therapy, the ability of the ImmTOR platform to enhance transgene expression, the ability of the Company and AskBio to develop gene therapy products using ImmTOR and AskBios core technology, the novelty of treatment paradigms that the Company and AskBio are able to develop, the potential of any therapies developed by the Company and AskBio to fulfill unmet medical needs, AskBios ability to make milestone payments, AskBios ability to develop and commercialize a drug product containing ImmTOR for the treatment of Pompe disease, the companys plan to apply its ImmTOR technology platform to a range of biologics for rare and serious diseases, the potential of the companys two gene therapy product candidates to enable repeat administration, the Companys ability to re-dose patients and the potential of ImmTOR to allow for re-dosing, the potential of the ImmTOR technology platform generally and the companys ability to grow its strategic partnerships, the Companys plans to present at the American College of Rheumatology Annual Meeting, the sufficiency of the companys cash, cash equivalents and short-term investments, and other statements containing the words anticipate, believe, continue, could, estimate, expect, hypothesize, intend, may, plan, potential, predict, project, should, target, would, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including, but not limited to, the following: the uncertainties inherent in the initiation, completion and cost of clinical trials including their uncertain outcomes, whether or not the COVID-19 outbreak will impact the companys ability to initiate a Phase 3 clinical trial for SEL-212 or to initiate a clinical trial in any of its gene therapy programs, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials, the unproven approach of the companys ImmTOR technology, potential delays in enrollment of patients, whether due to the COVID-19 outbreak or for other reasons, other issues surrounding the COVID-19 outbreak which may cause the company to discontinue or pause its ongoing or planned clinical trials, undesirable side effects of the companys product candidates, its reliance on third parties to manufacture its product candidates and to conduct its clinical trials who could be affected by the COVID-19 outbreak or could otherwise materially fail to perform, the companys inability to maintain its existing or future collaborations, licenses or contractual relationships, its inability to protect its proprietary technology and intellectual property, managements ability to perform as expected, potential delays in regulatory approvals, the availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements, the companys recurring losses from operations and negative cash flows from operations raise substantial doubt regarding its ability to continue as a going concern, substantial fluctuation in the price of its common stock, the impact of the COVID-19 outbreak on the companys operations, including its supply chain, clinical and financial operations, and other important factors discussed in the Risk Factors section of the companys most recent Annual Report on Form 10-K, and in other filings that the company makes with the Securities and Exchange Commission. In addition, any forward-looking statements included in this press release represent the companys views only as of the date of its publication and should not be relied upon as representing its views as of any subsequent date. The company specifically disclaims any intention to update any forward-looking statements included in this press release.

For Media:Joshua R. MansbachSolebury Trout+1-646-378-2964jmansbach@soleburytrout.com

For Investors:Lee M. SternSolebury Trout+1-646-378-2922lstern@soleburytrout.com

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Selecta Biosciences Appoints Dr. Goran Ando to its Board of DirectorsGlobal pharmaceutical and biotech industry veteran brings significant clinical...

A Tribute to Max Randell, Gene Therapy Pioneer – PLoS Blogs

I awoke on Monday morning to the sad news that Max Randell had passed away on April 18. He would have been 23 on October 9.

Maxie wasnt expected to live past the age of 8, or even much past toddlerhood, according to some doctors. But gene therapy, and his incredible family, had something to say about that. COVID-19 didnt claim him his body just tired of fighting.

Max Randells legacy is one of hope, to the rare disease community whose family members step up to participate in the clinical trials that lead to treatments. In this time of the pandemic, attention has, understandably, turned somewhat away from the many people who live with medical limitations all the time. Ill explore that story next week.

A Devastating Diagnosis

Max was diagnosed at 4 months of age with Canavan disease, an inherited neuromuscular disease that never touched his mind nor his ability to communicate with his eyes, even though his body increasingly limited what he could do. Fewer than a thousand people in the US have the condition.

Canavan disease is an enzyme deficiency that melts away the myelin that insulates brain neurons. Gene therapy provides working copies of the affected gene, ASPA.

Babies with Canavan disease are limp and listless. Most never speak, walk, or even turn over. Yet their facial expressions and responses indicate an uncanny awareness. A child laughs when his dad makes a fart-like noise; a little girl flutters her fingers as if they are on a keyboard when a friend plays piano. Theyre smart.

Today, with excellent speech, occupational, and physical therapy and earlier diagnosis, people with Canavan disease can live into their teens or twenties. Those with mild mutations live even longer.

Maxs passing is a tragedy, but he taught researchers about gene therapy to the brain. And that may help others.

Gene Therapy for Canavan

Max had his first gene therapy at 11 months of age and a second a few years later, after slight backsliding when clinical trials halted in the wake of the death of Jesse Gelsingerin a gene therapy trial for a different disease.

Ive written about Maxs journey through many editions of my human genetics textbook, in my book ongene therapy, and in several DNA Science posts, listed at the end.

Ive had the honor to attend two of Maxs birthday parties, which celebrate Canavan kids and the organization that his family founded, Canavan Research Illinois. At one party I brought along birthday cards that students whod read my gene therapy book made for him. And his grandma Peggy, who emailed me of his passing this past Monday, showed me how Max communicated with eyeblinks of differing duration and direction.

Heres what his mom Ilyce wrote about one yearly gathering:

This year will be the 20th Annual Canavan Charity Ball. Each year as I plan this event Im faced with the undeniable reality that theres a chance Maxie wont be here by the time the day rolls around. With each passing year this fear grows stronger and it becomes increasingly difficult to put into print that our annual event is in honor of Maxies birthday. Ive been talking to Maxie a lot lately about his life. He feels happy, strong, loved, content, productive, and fulfilled and he is looking forward to his upcoming 21st birthday. Im excited to celebrate this incredible milestone.

Maxs parents and brother Alex have had the unusual experience of time, of being able to watch their loved one as the years unfolded following gene therapy. They were able to see more subtle improvements than can the parents whose children have more recently had gene therapy to treat a brain disease. Parents watch and wait and hope that language will return, or that a child will become more mobile or less hyperactive, depending on the treated condition. The changes may be subtle, or slow, or restricted and thats what Max taught the world.

For him, the viruses that ferried the healing genes into his brain seem to have gathered at his visual system. His parents noticed improvements in the short term, just before his first birthday, as well as long term.

Within two to three weeks, he started tracking with his eyes, and he got glasses. He became more verbal and his motor skills improved. His vision is still so good that his ophthalmologist only sees him once a year, like any other kid with glasses. She calls him Miracle Max, Ilyce told me in 2010.

In 2016 I heard from Ilyce again:

I wanted to give you an update on Maxie. Hes going to be 19 on October 9th. He graduated from high school in June and is beginning a work program on Monday. Its been very exciting to watch him grow into a young man!

Max had an appointment with his ophthalmologist this week and his vision continues to improve. His doctor said that the gene is still active in his brain because his optic nerve shows absolutely no signs of degeneration and looks the same each year. I wish we could have been able to express the gene throughout more of his brain, but I am grateful for the treatments because of the progress hes made.

Even though gene therapy wasnt a cure for Max, the things we are experiencing definitely give me a lot of hope that once the delivery system is perfected, I can see a potential cure for Canavan disease in the future. Just knowing that the gene is still there 15 years later gives me confidence that a one-time gene transfer would actually work!

Maxs gene therapy circa 2002 targeted less than 1% of brain cells, with fewer viral vectors than are used to deliver healing genes in todays clinical trials. But it looks like some of the vectors may have made their way beyond the optic nerves, judging by the interest in math he had in high school and his critical thinking skills.

A Choice of Gene-Based Therapies

When the Randell family decided to pursue gene therapy, it was pretty much the only game in town. Thats changed.

Only two gene therapies have been approvedin the U.S. But a search at clinicaltrials.gov yielded 602 entriesdeploying the technology. The list still rounds up the usual suspects of years past mostly immune deficiencies, eye disorders, or blood conditions, with a few inborn errors of metabolism.

But one clinical trial mentions the gene-editing tool CRISPR, which can replace a mutant gene, not just add working copies as classical gene therapy does. TheCRISPRtrial is an experiment on stem cells removed from patients with Kabuki syndrome, which affects many body systems.

Spinal muscular atrophy now has two FDA-approved treatments, one an antisense therapy (Spinraza) that silences a mutation and the other (Zolgensma) a gene therapy that infuses copies of the functioning gene. Without treatment, the destruction of motor neurons in the spinal cord is usually lethal by age two.

In 2018, FDA approved the first drug based on RNA interference (RNAi), yet another biotechnology. It silences gene expression, which is at the RNA rather than the DNA level of the other approaches. Onpattro treats the tingling, tickling, and burning sensations from the rare condition hereditary transthyretin-mediated amyloidosis.

When I wrote my book on gene therapy in 2012, the technology was pretty much the only choice of research to pursue besides protein-based therapies like enzyme replacement. Now families raising funds for treatments for single-gene diseases can add antisense, RNAi, and CRISPR gene editing to the list of possibilities.

In any battle, a diversity of weapons ups the odds of defeating the enemy.

RIP Max Randell.

DNA Science posts:

Fighting Canavan: Honoring Rare Disease Week

A Brothers Love Fights Genetic Disease

Gene Therapy for Canavan Disease: Maxs Story

Celebrating the Moms of Gene Therapy

To support research:Canavan Research Illinois

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A Tribute to Max Randell, Gene Therapy Pioneer - PLoS Blogs

Vaccines, Antibodies and Drug Libraries. The Possible COVID-19 Treatments Researchers Are Excited About – TIME

In early April, about four months after a new, highly infectious coronavirus was first identified in China, an international group of scientists reported encouraging results from a study of an experimental drug for treating the viral disease known as COVID-19.

It was a small study, reported in the New England Journal of Medicine, but showed that remdesivir, an unapproved drug that was originally developed to fight Ebola, helped 68% of patients with severe breathing problems due to COVID-19 to improve; 60% of those who relied on a ventilator to breathe and took the drug were able to wean themselves off the machines after 18 days.

Repurposing drugs designed to treat other diseases to now treat COVID-19 is one of the quickest ways to find a new therapy to control the current pandemic. Also in April, researchers at Vanderbilt University enrolled the first patients in a much-anticipated study of hydroxychloroquine. Its already approved to treat malaria and certain autoimmune disorders like rheumatoid arthritis and lupus but hasnt been studied, until now, against coronavirus. Yet the medication has become a sought-after COVID-19 treatment after first Chinese doctors, and then President Trump touted its potential in treating COVID-19. The data from China is promising but not conclusive, and infectious disease experts, including Trumps coronavirus task force scientific advisor Dr. Anthony Fauci, arent convinced its ready for prime time yet in Americas emergency rooms and intensive care units.

But doctors facing an increasing flood of patients say they dont have time to wait for definitive data. In a survey of 5,000 physicians in 30 countries conducted by health care data company Sermo, 44% prescribed hydroxychloroquine for their COVID-19 patients, and 38% believed it was helping. Such off-label use in using a drug approved to treat one disease to treat another is allowed, especially during a pandemic when no other therapies are available. A similar percentage said remdesivir was very or extremely effective in treating COVID-19. (Although remdesivir is not approved for treating any disease, the Food and Drug Administration granted special authorization for doctors to use it to treat the sickest COVID-19 patients.)

That explains the unprecedented speed with which the hydroxychloroquine studyand others like itare popping up around the world. There are no treatments proven to disable SARS-CoV-2, the virus that causes the disease, which means all the options scientists are exploring are still very much in the trial-and-error stage. Still, they are desperate for anything that might provide even a slim chance of helping their patients survive, which is why studies are now putting dozens of different therapies and a handful of vaccines to the test. The normal road to developing new drugs is often a long oneand one that frequently meanders into dead ends and costly mistakes with no guarantees of success. But given the speed at which SARS-CoV-2 is infecting new hosts on every continent across the globe, those trials are being ushered along at a breakneck pace, telescoping the normal development and testing time by as much as half.

The newly launched Vanderbilt study, led by the National Heart, Lung, and Blood Institute of the U.S. National Institutes of Health, will enroll more than 500 people who have been hospitalized with COVID-19 and randomly assign them to receive hydroxychloroquine or placebo. It would be the first definitive trial to test whether hydroxychloroquine should be part of standard therapy for treating COVID-19, and its lead scientist expects results in a few months.

The sense of urgency is pushing other researchers at academic institutes as well as pharmaceutical companies to turn to their libraries of thousands of approved drugs or compounds that are in early testing and screening to see if any can disable SARS-CoV-2. Because these are either already approved and deemed safe for people, if any emerge as possible anti-COVID-19 therapies, companies could begin testing them in people infected with the virus within weeks. Other teams are mining recovered patients blood for precious COVID-19-fighting immune cells, and because the virus seems to attack the respiratory system, scientists are also finding clever ways to stop it from compromising lung tissue.

These are all stop-gap measures, however, since ultimately, a vaccine against COVID-19 is the only way to arm the worlds population against new waves of infection. Established pharmaceutical powers like Johnson & Johnson, Sanofi and Glaxo SmithKline are racing shoulder-to-shoulder to with startups using new technology to develop dozens of potential new vaccines, with the hope of inoculating the first people next yearnone too soon before what public health officials anticipate might be another season of either the same, or potentially new, coronavirus.

We know these viruses reside in animal species, and surely another one will emerge, says Dr. David Ho, director of the Aaron Diamond AIDS Research Center and professor of medicine at Columbia University, who is heading an effort to screen antiviral drug compounds for new COVID-19 treatments. We need to find permanent solutions to treating them, and should not repeat the mistake that once an epidemic wanes, interest and political will and funding also wanes.

Its an old-school approach that dates back to the late 19th century, but the intuitive logic behind using plasma from recovered patientstechnically called convalescent plasmaas a treatment might still apply today. Plasma treatments have been used with some success to treat measles, mumps and influenza. The idea is to use immune cells extracted from the blood of people who have recovered from COVID-19 and infuse them into those who are infected, giving them passive immunity to the disease, which could at least minimize some of its more severe symptoms.

Its part of a broader range of tactics that utilize the bodys own immune response as a molecular North Star for charting the course toward new treatments. And by far, antibodies against the virus are the most abundant and efficient targets, so a number of pharmaceutical and biotechnology companies are concentrating on isolating the ones with the strongest chance of neutralizing SARS-CoV-2.

In late March, New York Blood Center became the first U.S. facility to start collecting blood from recovered COVID-19 patients specifically to treat other people with the disease. Doctors at New Yorks Mount Sinai Health System are now referring recovered (and willing) patients to the Blood Center, which collects and processes the plasma and provides the antibody-rich therapy back to hospitals to treat other COVID-19 patients.. Its not clear yet whether the practice will work to treat COVID-19, but the Food and Drug Administration (FDA) is allowing doctors to try the passive immunity treatment in the sickest patients on a case by case basis, as long as they apply for permission to use or study the plasma an investigational new drug. If we can passively transfuse antibodies into someone who is actively sick, they might temporarily help that person fight infection more effectively, so they can get well a little bit quicker, says Dr. Bruce Sachais, chief medical officer at New York Blood Center Enterprises.

The biggest drawback to this approach, however, is the limited supply of antibodies. Each recovered donor has different levels of antibodies that target SARS-CoV-2, so collecting enough can be a problem, especially if the need continues to surge during an ongoing pandemic. At the Maryland-based pharmaceutical company Emergent BioSolutions, scientists are trying to overcome this challenge by turning to a unique source of plasma donors: horses. Their size makes them ideal donors, says Laura Saward, head of the companys therapeutic business unit. Scientists already use plasma from horses to produce treatments for botulism (a bacterial infection), and have found that the volume of plasma the animals can donate means each unit can treat more than one patient (with human donors, at this point, one unit of plasma from a donor can treat one patient). Horses plasma may also have higher concentrations of antibody, so the thought is that a smaller dose of equine plasma would be effective in people because there would be higher levels of antibody in smaller doses, says Saward. By the end of the summer, the company expects its equine plasma to be ready for testing in people.

Scientists are also looking for other ways to generate the virus-fighting antibodies produced by COVID-19 patients. At Regeneron, a biotechnology firm based in New York, researchers are turning to mice bred with human-like immune systems and infected with SARS-CoV-2. Theyre searching hundreds of antibodies these animals produce for the ones that can most effectively neutralize the virus. By mid-April, the company plans to start manufacturing the most powerful candidates and prepare them (either solo or in combination) for human testingboth in those who are already infected, as well as in healthy people, to protect from getting infected in the first place, like a vaccine.

Its not just people and animals that can produce antibodies. Scientists now have the technology to build what are essentially molecular copying machines that can theoretically churn out large volumes of the antibodies found in recovered patients. At GigaGen, a San Francisco-based biotech startup founded by Stanford University professor Dr. Everett Meyer, scientists are identifying the right antibodies from recovered COVID-19 patients and hoping to use them as a template for synthesizing new ones, in a more consistent and efficient way so a handful of donors could potentially produce enough antibodies to treat millions of patients. What GigaGens technology does is almost Xerox copy a big swath of the human repertoire of antibodies, and then takes those copies and grows it in cells [in the lab] to manufacture more antibodies outside of the human body, says Meyer. So we can essentially keep up with the virus. If all goes well and the FDA gives its green light, the company intends to start testing their antibody concoctions in COVID-19 patients early next year.

Researchers at Rockefeller University are following another clue from the human bodys virus-fighting defenses. They discovered in 2017 that human cells make a protein called LY6E that can block a viruss ability to make copies of itself. Working with scientists at the University of Bern in Switzerland and the University of Texas Southwestern Medical Center, they found that mice genetically engineered to not produce the protein became sicker, and were more likely to die after infection with other coronaviruses, including SARS and MERS, compared to mice that were able to make the protein. If the mice have the protein they pretty much survive, says John Schoggins, associate professor of microbiology at the University of Texas. If they dont have it, they dont survivebecause their immune system cant control the virus. While these studies havent yet been done on SARS-CoV-2, given its similarity to the original SARS virus, theres hope a therapy based on LY6E might be useful.

Ideally, Schoggins is hoping to start testing LY6Es potential in infected human lung cells, which SARS-CoV-2 appears to target for disease. The closest mouse model for coronavirus, created to study the original SARS virus, has been retired since research on that virus dwindled after cases wanted following the 2003 outbreak. There wasnt the need to keep the mouse around, and that tells us a lot about the state of our research, says Schoggins. We dont really work on thing unless everyones hair is on fire.

Its not just immune cells that make good targets for new drugs. Other companies are looking at broader immune-system changes triggered by stressduring cancer, for example, or infection with a new virus like SARS-CoV-2that end up making it easier for a virus to infect cells. Drugs that inhibit these stress-related changes would act like molecular gates slamming shut on the cells that viruses are trying to infect.

Because SARS-CoV-2 preferentially attacks lung tissue and causes cells in the respiratory tract to launch a hyperactive immune response, researchers are exploring ways to tame that aggressive response by dousing those cells with a familiar gas: nitric oxide, often used to relax blood vessels and open up blood flow in hospital patients on ventilators who have trouble breathing. While working on a new, portable system for delivering nitric oxide developed by Bellerophon Therapeutics to treat a breathing disorder in newborns, Dr. Roger Alvarez, an assistant professor of medicine at University of Miami, got the idea that the gas might be helpful for COVID-19 patients as well. One symptom of the viral infection is low oxygen levels in the lungs, and nitric oxide is ideally designed to grab more oxygen molecules from the air with each breath and feed it to the lungs. With this system, patients dont need to be in the ICU [Intensive Care Unit] at all, he says. The patient can be in a regular hospital bed, or even at home. So you save the cost of the ICU and from a resource standpoint, you save on needing nursing care, respiratory therapists and other ICU monitoring.

In theory, if this system could be used for COVID-19 patients with moderate symptoms, it could keep those patients from needing a ventilatora huge benefit in the current context where ventilator shortages are one of the biggest threats to the U.S. health care system. So far, Alvarez has received emergency use authorization from the FDA to test a version of his system on one COVID-19 patient at the University of Miami Health System. That patient improved and is ready to go home. Its great news and gives me the information to say that this appears at least safe to study further, he says, which is what he plans to do with the first small trial of nitric oxide for COVID-19 at his hospital.

When it comes to developing a new antiviral treatment, it doesnt always pay to start from scratch. There are dozens of drugs that have become life-saving therapies for one disease after their developers accidentally discovered that the medications had other, equally useful effects. Viagra, for example, was originally explored as a heart disease drug before its unintended effect in treating erectile dysfunction was discovered, and gabapentin was developed as an epilepsy drug, but is now also prescribed to control nerve pain.

Within weeks of COVID-19 cases spiking to alarming levels in China, researchers at Gilead in Foster City, Cal., saw an opportunity. A drug the company had developed against Ebola, remdesivir, had shown glimmers of hope in controlling that virus in the laband also showed promise as a tool to treat coronaviruses like those that caused SARS and MERS. In fact, says Merdad Parsey, chief medical officer of Gilead, We knew in the test tube that remdesivir had more activity against coronaviruses like SARS and MERS than against Ebola. So it wasnt entirely surprising that when the company began testing it in people during last years Ebola outbreak in the Democratic Republic of Congo, the results were disappointing. The early studies against Ebola werent as encouraging in people as they were in animals. So we were basically on hold with the drug, waiting to see if there would be another [Ebola] outbreak to see if we could test it earlier in the infection, says Parsey.

Then COVID-19 happened. As the infection roared through Wuhan, Chinathe original epicenter of the diseaseresearchers there reached out to Gilead, knowing that the company had released data suggesting that remdeisivir had strong antiviral effects in lab studies against coronaviruses. They launched two studies of the drug in the sickest patients.

In mid-January, a man in Everett, Wash., who had recently visited Wuhan, checked into a clinic after a few days of feeling sick. He quickly went from having a fever and cough to having difficulty breathing because of pneumonia. Concerned that the man was worsening by the day, his doctor contacted the U.S. Centers for Disease Control; suspecting this might be a case of COVID-19and knowing there was no proven treatment for the infectionexperts at the agency suggested he try an experimental therapy, remdesivir.

The CDC team felt relatively confident about the drugs safety, if not its effectiveness, since Gilead had studied it extensively in animal models and, in the early trials in people, it didnt lead to any serious side effects and appeared safe. They were also aware of the companys promising data with human cells against the original SARS.

For the Washington patient, the experimental drug might be a lifesaver. A day after receiving remdesivir intravenously, his fever dropped, and he no longer needed supplemental oxygen to breathe. About two weeks after entering the hospital, he was discharged to self-isolate for several more days at home.

That set off a rush for remdesivir as cases in the U.S. went from a trickle to a flood, and doctors grasped for anything to treat quickly declining patients. Gilead initially offered the drug on a compassionate use basis, a process that allows companies, with the FDAs permission, to provide unapproved drugs currently being studied to patients who need them as a last resort. These programs are designed for one-off uses, and companies usually receive two to three requests a month from doctors . But in this case, Gilead was flooded with requests for remdesivir at the beginning of March. And because each one is evaluated on a case-by-case basis to ensure that each patient is eligible and that the potential risks of trying an untested drug dont outweigh the benefits, a backlog developed and the company couldnt respond to the requests in a timely way, says Parsey. So on March 30, Gilead announced it would no longer provide remdesivir through that program but through an expanded access program instead. Doctors can get access to the drug for their COVID-19 patients via dozens of clinical trials of remdesivir, two of which Gilead initiated. One is focused on patients with mild symptoms and one involves those with severe symptoms. The National Institutes of Health is currently heading another large study of the drug, at multiple centers around the country.

Finding a new purpose for existing drugs is ideal; they are likely already proven safe and their developers have a substantial dossier of information on how the drugs work. Thats what happened with hydroxychloroquine, a malaria drug developed after the parasite that causes the illness became resistant to the chloroquine, a drug discovered during World War II and since used widely to fight the disease. As researchers studied hydroxychloroquine in the lab in recent decades , they learned it can block viruses, including coronaviruses, from infecting cells. In lab studies, when researchers infected human cells with different viruses and then bathed them in hydroxychloroquine, those cells could generally stop viruses like influenza, SARS-CoV-2, and the original SARS virus, another type of coronavirus, from infecting the cells. The problem is that what happens in the lab often doesnt predict what happens in a patient, says Dr. Otto Yang, from the department of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at the University of California Los Angeles. In fact, in the case of influenza, the drug wasnt as successful in stopping infection in animals or in people. Similarly, when scientists brought hydroxychloroquine out of the lab and tested it in people, the drug failed to block infection with HIV and dengue as well.

Thats why doctors are approaching hydroxychloroquine with healthy skepticism when it comes to COVID-19 and are only using it on the sickest patients with no other options. Doctors at a number of hospitals, including Johns Hopkins, the University of California Los Angeles, and Brigham and Womens, for example, are starting to use hydroxychloroquine to treat patients with severe COVID-19 symptoms when they dont improve on current supportive treatments. Its not ideal, but If someone is sick in the ICU you try everything possible you can for that person, says Dr. David Boulware, a professor of medicine at the University of Minnesota, who is conducting a study of hydroxychloroquine effectiveness both in treating those with severe disease and in protecting health people from infection.

Other researchers are attempting to trace the same path with other repurposed drugs, including a flu treatment from Toyama Chemical, a pharmaceutical division of the Japanese conglomerate Fujifilm, called favipiravir, which Chinese researchers used to treat patients with COVID-19. More rigorous studies of both remdesivir and favipirivir against SARS-CoV-2 are ongoing; all researchers can say at this point is that they are worth studying further, and that they appear to be safe.

Even cancer drugs are showing promise as COVID-19 treatments, not by neutralizing the virus but by healing the damage infection does to the immune system. The Swiss pharmaceutical giant Novartis, for example, has ruxolitinib (sold under the trade name Jakavi), which was approved by the FDA in 2011 to treat a number of different cancers, and is designed to tamp down an exaggerated immune responsewhich can be caused by both tumor cells and a virus. In the case of SARS-CoV-2, a hyperactive immune response can trigger breathing problems, called a cytokine storm, that require extra oxygen therapy or mechanical ventilation. In theory, ruxolitinib could suppress this virus-caused cytokine storm. Novartis is making its drug available on an emergency use basis for doctors willing to try it on their sickest patients.

Eli Lilly is also testing one of its anti-inflammatory drugs, baricitinib, in severe COVID-19 patients. Like ruxolitinib, baricitinib interferes with the revved up signalling among immume cells that can trigger the inflammatory cytokine storm. According to president of Lilly Bio-Medicines Patrik Jonsson, there are even early hints from case studies of doctors treating COVID-19 patients that the drug may target the virus too, which could mean that it helps to lower the viral load in infected patients. The company is working with NIAID to confirm whether this is the case in a more rigorous study of severe COVID-19 patients, and expects to see results by summer.

It wasnt immediately obvious that baricitinib could potentially treat COVID-19; it took an artificial intelligence effort by UK-based BenevolentAI to scour existing medical literature and descriptions of drug structures to identify baricitinib as a possible therapy.

Such machine learning-based techniques are making the search for new therapies far more efficient than ever before. Chloroquine, hydroxychloroquines parent, came out of a massive war-time drug discovery effort in the 1940s, when governments and pharmaceutical companies combed through existing drug libraries for promising new ways to treat malaria. With computing power that is orders of magnitude greater now, its now possible to single out not just existing drugs with antiviral potential, but entirely new ones that may have gone unnoticed.

When Sumit Chanda first heard of the mysterious pneumonia-like illnesses spiking in Wuhan, China, he had an eerie feeling that the world was about to face a formidable viral foe. He had spent his entire career studying all the clever and devilish ways that bacteria, viruses and pathogens find hospitable hosts and then take up residence, oblivious to how much illness, disease and devastation they may cause. And as director of the immunity and pathogenesis program at Sanford Burnham Prebys Medical Discovery Institute in San Diego, Chanda knew that if the mystery illness striking in China was indeed caused by a new virus or bacteria, then doctors would need new ways to treat itand quickly.

So, he and his team started canvassing a 13,000 drug library, which is funded by the Bill and Melinda Gates Foundation and created by Scripps Research. Our strategy is to take existing drugs and see if they might have any efficacy as an antiviral to fight COVID-19, he says. The advantage of this approach is that you can shave years upon years off the development process and the studies on safety. We want to move things quickly into [testing] in people. In a matter of weeks, he has narrowed down the list of potential coronavirus drug candidates, and because these are already existing drugs and approved for treating other diseases, they are relatively safe, and can quickly be tested in people infected with SARS-CoV-2.

Chandas team isnt the only one taking advantage of this approach. Researchers at numerous pharmaceutical companies, biotech outfits and academic centers are screening their libraries of drugsboth approved and in developmentfor any anti-COVID-19 potential.

At Columbia University, Dr. David Ho, who pioneered ways of creating cocktails of drugs to make them more potent against HIV, is scouring a different library of virus-targeting drugs to pluck out ones that could be effective against SARS-CoV-2. Altogether, he has some 4,700 drugs (approved and in development) to look through, and he believes there is a strong chance of finding something that might be effective against not just SARS-CoV-2 but any other coronavirus that might pop up in coming years. The key, says Ho, is to be prepared for the next outbreak so the work on finding antiviral drugs doesnt have to start from scratch. We know these viruses reside in animal species, he says. We predict in the coming decade there will be more [outbreaks]. And we need to find permanent solutions. We should not repeat the mistake we made after SARS and after MERS, that once the epidemic wanes, the interest and the political will and the funding also wanes. If we had followed through with the work that had begun with SARS, we would be so much better off today.

But today, we are in the midst of a pandemic, and scientists are eager to leave no potentially promising technology untried. Banking on the growing body of science looking at how newborn babies are able to avoid life-threatening infections in their first days in the world, researchers at New Jersey-based Celularity are investigating how placental cells, rich with immune cells that protect the baby in utero, might also become a source of immune defense therapy against COVID-19. Its part of a broader strategy of cell-based treatments that scientists are beginning to explore for treating cancer as well as infectious disease.

On April 1, the company received FDA clearance for its placental cell treatment, based on a group of immune cells called natural killer cells that circulate in the placenta, and are designed to protect the developing fetus from infection. They are programmed to recognize red flags typically sent up by cells infected with viruses like SARS-CoV-2, and destroy them. After the 2002-2003 SARS epidemic, researchers in China found that people who had more severe symptoms of that disease also had deficient populations of natural killer cells.

The FDA green light means the company can launch a small human study using placental natural killer cells against COVID-19. Dr. Robert Hariri, Celularitys founder and CEO, wants to test them first in people who are infected, to see if they can stop the infection from getting worse. Our approach is to flatten the immunologic curve, he says. Our hope is to decrease the size of the viral load and keep it below the threshold of serious symptomatic disease until the patients own immune system can be revved up and respond. If those studies are encouraging, then the company will look at how natural killer cells might be used to pre-charge the immune system to prevent infection with SARS-CoV-2 in the first place.

As effective and critical as these therapies might be, they are a safety net for the best weapon against an infectious disease: a vaccine.

The main reason that a new virus like SARS-CoV-2 has such free license to infect hundreds of thousands of people around the world is because its an entirely new enemy for the human immune system making the planets population an open target for infection. But a vaccine that can prime the body to build an army of antibodies and immune cells trained to recognize and destroy the coronavirus would act as an impenetrable molecular fortress blocking invasion and preventing disease.

Unfortunately, vaccines take time to developyears, if not decades. Scientists at Johnson & Johnson are currently working on a vaccine using fragments of the SARS-CoV-2 spike protein, an easy protein target that sprinkles the surface of the virus like a crown (hence the name coronavirus, from the Latin for crown). The company loads the viral gene for the spike protein into a disabled common-cold virus vector that delivers the genetic material to human cells. The immune system then recognizes the viral fragments as foreign and deploys defensive cells to destroy it. In the process, the immune system learns to recognize the genetic material of the virus, so when the body is confronted by the actual virus, its ready to attack.

Given the manufacturing requirements to build the vaccine, and the studies in animals needed to get a hint of whether the vaccine will work, however, J&Js project is unlikely to come to fruition until mid-2021. We plan to have the first data on the vaccine before the end of the year, says Paul Stoffels, chief science officer at J&J. I would hope that in the first half of next year, we should be able to get vaccines ready for people in high risk groups like health care workers on the front lines.

That timeline is already accelerated quite a bit compared to vaccine research in non-pandemic contexts. But new technology that doesnt require a live transport system could shrink the time to human tests even further. Working with the National Institute of Allergy and Infectious Diseases, Moderna Therapeutics, a biotech based in Cambridge, Mass., developed its mRNA vaccine in a record 42 days after the genetic sequence of the new coronavirus was released in mid January. Its system turns the human body into a living lab to churn out the viral proteins that activate the immune system.

Researchers at Moderna hot wired the traditional vaccine-making process by packing their shot with mRNA, the genetic material that comes from DNA and makes proteins. The viral mRNA is encased in a lipid vessel that is injected into the body. Once inside, immune cells in the lymphatic system process the mRNA and use it like a genetic beacon to attract immune cells that can mount toxic responses against the virus. Our vaccine is like the software program for the body, says Dr. Stephen Hoge, president of Moderna. So which then goes and makes the [viral] proteins that can generate an immune response.

Because this method doesnt involve live or dead virusesall it requires is a lab that can synthesize the correct genetic viral sequencesit can be scaled up quickly since researchers dont have to wait for viruses to grow. Almost exactly two months after the genetic sequence of SARS-CoV-2 was first published by Chinese researchers, the first volunteer received an injection of the Moderna vaccine. The companys first study of the vaccine, which will include 45 healthy participants, will monitor its safety. Hoge is already gearing up to produce hundreds and thousands of more doses to prepare for the next stage of testing, which will enroll hundreds of people, most likely those at high risk of getting infected, like health care workers.

If those results arent as promising as health experts hope, there are other innovative options in the works. At the University of Pittsburgh, scientists who had been developing a vaccine against the original SARS virus have switched to making a shot against the new one. Their technology involves hundreds of microneedles in a band-aid like patch that deliver parts of the coronavirus protein directly into the skin. From there, the foreign viral proteins are swept into the blood and into the lymph system, where immune cells recognize them as invaders and develop antibodies against them. After seeing animals inoculated with their vaccine develop strong antibodies against SARS-CoV-2, the team is ready to submit an application to the FDA to begin testing in people.

Whats different about these new coronavirus efforts is the fact that they arent all designed to control SARS-CoV-2 alone. Recognizing that this coronavirus is the third in recent decades to cause pandemic disease, scientists are focusing on building therapies, including vaccines, that can quickly be adapted to target different coronaviruses that might emerge in coming years. We hope these new technologies become the kinds of things we build in our tool kits that as humans will allow us to respond in a much more accelerated way to the next pandemic, says Modernas Hoge. Because we expect continuing threats from viruses in the future.

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Vaccines, Antibodies and Drug Libraries. The Possible COVID-19 Treatments Researchers Are Excited About - TIME

Sharpless: NCI is fully operational, we have a moral obligation to help in the COVID-19 pandemic response – The Cancer Letter

publication date: Apr. 14, 2020

By Matthew Bin Han Ong

This story is part of The Cancer Letters ongoing coverage of COVID-19s impact on oncology. A fulldirectory of our coverage is availablehere.

In spite of disruptions caused by the coronavirus pandemic, NCI continues to review grants, disburse funds, and support extramural research, said NCI Director Ned Sharpless.

I really wont sugarcoat our present circumstances. This epidemic is bad, and its going to continue to be bad for a while, especially the next few weeks, Sharpless said April 9 in an emergency virtual meeting of the NCI Board of Scientific Advisors and the National Cancer Advisory Board. We have suspended lab operations on campus and we have stopped all non-essential activities.

But I want to reiterate right now, from an extramural funding point of view, we are fully operational. But, no doubt, things have gotten more complicated, and we have received many, many questions from our investigators about grants, lab suspensions, and what this all means for them.

When we do reach uniform agreement about these funding policies, the NCI is fully committed to disseminating that information as quickly as possible through blogs, our website, Twitter streams, etc.

Thus far, two lessons for U.S. health care and oncology can be derived:

Weve shown that, in a meaningful way, we can take care of patients via telehealth, and I predict cancer patients are going to like this in the future, Sharpless said. Another area where Ive seen a real example of something that, I think, will last after the pandemic, for the good, is the fact that the government can, when it needs to, move really quickly.

We have been involved in complex multi-agency endeavors, but weve been able to really cut through a lot of the process and the usual steps to launch large, innovative, complex research efforts in a matter of days.

The institute, with its research capabilities, has a moral obligation to be involved in the U.S. national response to the pandemic, Sharpless said.

NCI has a long and storied history of intramural virology research, from Doug Lowy and John Schiller and Harold Varmus, to Bob Gallo, to Sam Broderpathbreaking, groundbreaking work on HPV and HIV and RNA tumor virusesand to not use the virology expertise at the NCI during the current pandemic would seem to be a missed opportunity, Sharpless said.

NCI is finalizing plans to use its clinical trials networks to administer a compassionate use protocol for distribution of tocilizumab, a drug that blocks the inflammatory protein IL-6. Under the institutes protocol, the drug will be made available to cancer patients at institutions that are not participating in Genentechs phase III trial of the drug (The Cancer Letter, April 10, 2020).

Other updates at NCI include:

Enrollment of the first patient in a CD33 CAR T trial, a collaboration between the institute and the Childrens Hospital of Philadelphia; and

Appointment of Dan Gallahan as director of the Division of Cancer Biology.

On March 27, Congress passed a $2 trillion coronavirus relief package, the Coronavirus Aid, Relief and Economic Security (CARES) Act. The bill appropriates pandemic response funds in the following amounts: $4.3 billion for CDC, $945.4 million for NIH, $80 million for FDA, and $200 million for CMS (The Cancer Letter, March 27, 2020).

The Congress has done some stuff for coronavirus, Sharpless said. Most probably relevant for the NIH is phase 3, the CARES Act, which provided significant new money for the NIH as well as the FDA and CDC, and it alsoan issue Im sure very important to many of the board membersprovided significant funding for hospitals, given the massive drop in revenues some hospitals are seeing with the cessation of elective surgeries and that type of issue.

Normalcy will return, Sharpless assured the advisory boards.

Im here to tell you well get through this, he said. And this is going to be a tough period for the NCI, for cancer research, but it will come to an end.

Sharplesss remarks to BSA and NCAB follow:

Welcome to our first-ever virtual joint board meeting. This is an emergency meeting that I called to discuss the NCIs response to the coronavirus pandemic. Thank you to all of you for making time. The pandemic has no doubt scrambled your schedules and I really appreciate your being available on short notice. NCI really needs your advice on some complex issues.

Well have talks by Doug Lowy, Dafna [Bar-Sagi] and Jim [Doroshow], and in a closed session Dinah [Singer] will have some further remarks. As noted, there will be time for discussion after the remarks, this is a vital part of todays meeting. Im sure we will all be saying many times today, Could you please all mute? as with my experience with prior WebExs.

One thing I want to make clear from the outset is that this is an emergency meeting to discuss the NCI response to the pandemic. And, necessarily, were going to be talking a lot about the coronavirus pandemic, but I want to make very clear right now that the primary focus of the National Cancer Institute is on cancer research and cancer care. That is our primary focus for now and forever. And this meeting will not supplant other scheduled NCAB or BSA meetings where we will continue to talk more about usual NCI business in those meetings.

Id like to reiterate the points on the slide here that cancer research and cancer care remain job number one at NCI, even though our operations have been somewhat disrupted by the pandemic. And even during these difficult times, I think we are still making progress toward our mission of reducing cancer suffering.

But today is an emergency meeting to talk about a crisis that has gripped our nation and disrupted our work. And Im sure many of you would agree the National Cancer Institute has to be involved in the pandemic response. NCI has unique research capabilities and capacities, so, to help in this complex situation, we believe, is a moral obligation.

First off, the NCI has a long and storied history of intramural virology research, from Doug Lowy and John Schiller and Harold Varmus, to Bob Gallo to Sam Broderpathbreaking, groundbreaking work on HPV and HIV and RNA tumor virusesand to not use the virology expertise at the NCI during the current pandemic would seem to be a missed opportunity.

Also, the Frederick National Lab, which the NCI administers in collaboration with [the National Institute of Allergy and Infectious Diseases], has unique capabilities and resources that are really tailor-made for an emergency situation like this. The facilities at the Frederick Lab are quite exceptional, like the cryo-EM facility and the serology lab that can be useful and deployed in the current pandemic.

Frederick National Lab has unique contracting authorities that allow it to move very quickly to set up new research as needed. And it has the ability to form robust collaborative relationships, both with extramural scientists as well as industry. And so for these reasons its really well suited to take on the coronavirus pandemic. And Doug Lowy will be talking about many of the ways weve been using Frederick National Lab in conjunction with NIAID during the present crisis.

And then, lastly, the NCI supports the worlds best scientists bar none, and through our extramural funding programs, and thats through our networks and our individual investigator-initiated grants, and these individuals have tremendous research capabilities and skills that can be very useful in a pandemic. So, not to involve the extramural fundees would seem, also, a missed opportunity. And we have heard a lot from you on this question.

Ive had many conversations and emails with cancer center directors and scientists, with clinicians, with trainees at the various cancer centers about what you can do to work on the coronavirus pandemic and how the NCI can support those efforts. And thank you for giving us that feedback, and thank you for volunteering your expertise. In short, because of these reasons and others, we believe the NCI has important contributions to make during the coronavirus pandemic.

Just as the pandemic, no doubt, has changed operations at your institution, it has radically changed how the NIH and the NCI operate. Were still able to keep research going while complying with physical distancing. One of our awesome WebExs is to do a senior weekly leadership meeting by this format and how well that works. We have suspended lab operations on campus and we have stopped all non-essential activities.

But the clinical center is still operationaltreating patients, including cancer patients, with lifesaving therapies. It has reduced elective procedures and has taken in some COVID-19 patients, but it still continues to work, and NCI staff work there under, as you can imagine, difficult circumstances.

In order to reconfigure a 3,000-personnel organization with thousands of contractors in such a rapid capacity is really a challenge, but Ive been thrilled and impressed by how much weve been able to do, even virtually. Im also very excited to see how cross-government collaborations have sprung up in a very rapid and direct manner, both across the NIH and the rest of federal government.

In the last few weeks, the NCI has started very important mutual research efforts with NIAID, with [the National Institute of Biomedical Imaging and Bioengineering], with [the National Heart, Lung, and Blood Institute], and with the Aging Institute. We are also working very intimately with other federal agencies, including the FDA, the CDC, BARDA, and other parts of the HHS.

One other point Ill make is that although the pandemic has disrupted operations, I believe we will take some very valuable and meaningful things from this experience. Some of the changes that are being inflicted upon us may actually lead to some good overall.

Two important examples: the first, I believe telehealth is here to stay. Weve shown that, in a meaningful way, we can take care of patients via telehealth, and I predict cancer patients are going to like this in the future. Theyre going to like the ability to see their doctor sometimes virtually, rather than in person.

And by the way, I will mention now that this is a tremendous pop-sci research opportunity. If youre studying implementation science, your moment has arrived, because a thing like this where weve gone from nobody using telehealth to a large part of the country using telehealthin, really, a couple of daysis a tremendous change in our practice, and really will lead to some great research, I believe.

Another area where Ive seen a real example of something that, I think, will last after the pandemic, for the good, is the fact that the government can, when it needs to, move really quickly. We have been involved in complex multi-agency endeavors, but weve been able to really cut through a lot of the process and the usual steps to launch large, innovative, complex research efforts in a matter of days.

Jim Doroshow will talk about some of the clinical trials the NCI has recently stood up. I think these are some of the fastest trials that weve ever gotten started at the NCI in our history, and Doug Lowy will talk about many of the efforts at Frederick National Lab, including a serology effort theyre working with the FDA, it just has to be seen to be believed what theyve started in just a few weeks (The Cancer Letter, April 10, 2020).

We also wont cover everything the NCI is doing. It is just too much. We really have too many activities in this space, so I wont really talk about our work with BARDA or what were doing in the SBIR program with small companies that work on coronavirus, or a very interesting set of collaborations with the NIBIB on a novel data platform that is aimed to help people get back to work.

But we will focus on a few of the more visible efforts in later talks. I hope that as life gets back to normal, we in the federal government can take these lessons were learning from the pandemic about how to do business differently and that will help cancer research in the future.

Im pleased to report that the NCIs Cancer Information Service, 1800-4-CANCER is fully operational and has been up continuously throughout the pandemic, even though its gone remote. Weve already received hundreds of inquiries related to the coronavirus, as of yesterday. Most of the questions from cancer patients for their loved ones involve questions about risk and whether they are considered immunocompromised, whether their cancer puts them in increased risk.

As you can imagine, the nature of calls to 1800-4-CANCER really has changed during the pandemic. We get questions now like, Should I go to my doctor? Can I get my scheduled chemotherapy? Can I get a blood transfusion? Im sure your institutions are dealing with these same questions. The Cancer Information Service is a highly visible service of the NCI that we provide for patients and it is moving along rapidly and working fully in a full capacity, even during the pandemic.

Weve also produced some new key resources for patients and caregivers. A few examples are shown here. So, we stood up a coronavirus page with information for people with cancer as of March 13, that website has already received more than 60,000 visits. Its the fourth most-visited page on our website. In addition, we have also stood up a coronavirus page targeted to researchers as of March 25, and that website has received 1,400 visits and well provide these links in the material for the meeting and they can also be easily accessed from cancer.gov.

In addition, were trying to maintain really strong communications to our research community. Theres been lots of internal communications. I did a virtual town hall meeting using the similar format to this that had 4,000 live attendees.

Here, Im highlighting some of our external communications efforts: weve done cancer.gov websites, as I mentioned, weve had several blogs, weve done social media through many of our Twitter accounts, including the highly popular NCI Director account.

We really want people to understand whats going on with grants and other funding matters. I had an NCI Bottom Line blog post on NCI funding during the coronavirus pandemic thats received 5,500 visits since its publication on March 23, and it has some useful information for extramural fundees, and I commend it to all of you.

Also, Oliver Bogler has written a Bottom Line blog post about training grant issues, K awards, and F awards, and T awards and their deadlines and their reporting requirements, and how the NCI is going to handle those issues. Thats up now, and I commend it to all of you. In summary, were trying to maintain communications to all our stakeholders, NCI employees, researchers, caregivers, and most importantly, patients throughout the time of the pandemic.

The coronavirus has really affected how we do business at the NCI and, no doubt, how you do business at your institutions. But I want to reiterate right now, from an extramural funding point of view, we are fully operational. We are up and running, we can review grants, we can disburse funds, we can do what we normally need to do to support the extramural research community. But, no doubt, things have gotten more complicated, and we have received many, many questions from our investigators about grants, lab suspensions, and what this all means for them.

Cancer center directors, trainees, postdocs, integrated research programs, individual scientists have all been asking us lots of questions and Ive listed some of the key issues here, like deadlines for applications and the use of funds and flexibility around reporting requirements and extensions for training periods. And let me say, I provided some material in advance from the Office of Extramural Research, Mike Lauers office at the NIH, that has a lot of really great information in that document, recently updated and is current, and I commend it to all of you, because it talks about a lot of these issues in detail.

Certainly, we can talk about any one of these more in a Q&A, if theres interest. But I will say, as a general principle, the NCI is trying to provide maximal flexibility to investigators so they can get their important work done during this crisis. We really want to avoid work stoppages, we want to avoid layoffs, we want to avoid a loss of the research capacity for cancer research in the United States.

Although, it has to be acknowledged that the policies we adopt at the NCI have to fit within policies of the greater federal government, we cannot really go it alone on extramural grant policies, as what we do has to agree with what the NIH and other grant making organizations within the federal government do.

But when we do reach uniform agreement about these funding policies, the NCI is fully committed to disseminating that information as quickly as possible through blogs, our website, Twitter streams, etc.

Its also important to note that we have a number of funding opportunities both not related to coronavirus, and I think those are out and probably familiar to many of you, and we also expect to have some coronavirus-related funding opportunities appearing soon, so please stay tuned for that.

We have some good news from a leadership point of view here at the NCI. Dan Gallahan, after being acting director of the Division of Cancer Biology for a while, has now become the director of the Division of Cancer Biology. We have really benefited from Dans leadership, and NCI is very lucky to have Dan in this role, which is tremendously important for the NCI. I would like to give a round of virtual applause for Dan Gallahan. Hey, alright, that worked!

I would also like to thank Dinah Singer, who held this position prior to Dan. She has now moved to become the deputy director of the NCI, and as I mentioned, well be hearing from Dinah later on some important topics related to the NCIs extramural programs.

It is clear that Congress is extremely interested in our activities during the coronavirus pandemic. This is a hearing that was held on March 4that was like a month agoLabor-HHS subcommittee for the House Appropriations Committee, where there were a lot of questions about how the United States is responding. Doesnt this really seem like a lifetime ago? I mean, here we all were, packed in a room, close together, not wearing masks, talking to each other. I had hair back then, that was a while ago.

Sitting beside me, by the way, is Americas most famous scientist, Tony Fauci [director of NIAID]. I think Tony and I have had a very close working relationship my entire time at the NCI, but it has really gotten a lot closer, because of the joint NIAID-NCI activities during the pandemic, and I think the nation as a whole is so lucky to have Tonys leadership during this time. He is a remarkable American institution.

At this hearing, as you can imagine, there was a tremendous amount of questions about the coronavirus and the pandemic, but also this is the subcommittee, I remind you, chaired by Rosa DeLauro (D-CT) and Tom Cole (R-OK).

There was a lot of interest in cancer research. That group is very committed to cancer science and we had some great discussions about cancer research, paylines, pediatric cancer, clinical trials and many other topics. So, while Congress is very interested in coronavirus for the moment, they are consistently also very interested in supporting cancer research as they have done generously for a while.

I would say this congressional interest since this March 4 hearing has significantly even further intensified. Over the last week alone, I have spoken with, I think, maybe three or four senators and representatives about NCI activities related to the pandemic, and also with various staff for the House and the Senate, and these conversations really continue.

The Congress has done some stuff for coronavirus. Shown here are three fairly large supplemental spending packages that have moved rapidly through Congress to support a number of things regarding science and patient care, and the American economy. Most probably relevant for the NIH is phase 3, the CARES Act, which provided significant new money for the NIH as well as the FDA and CDC, and it alsoan issue Im sure very important to many of the board membersprovided significant funding for hospitals, given the massive drop in revenues some hospitals are seeing with the cessation of elective surgeries and that type of issue.

Another thing we just learned recently is the FDA position regarding the CARES Act, which has a provision that all Americans can get testing for the coronavirus. And as I said, the FDA interprets that to mean both RT-PCR testing for the coronavirus as well as serologic IgG, IgM antibody testing for the coronavirus. This has very significant implications for the Frederick National Lab serology effort that Doug Lowy will be talking about later. Theres also talk, Im sure many of you heard, about the possibility of a fourth supplemental spending bill. Should that happen, there is a good chance, I think, that there will be funding in that for the NIH and for the clinical center.

I really couldnt resist, as I said, even though you know its a lot of coronavirus going on around here right now, cancer really does continue at a brisk pace despite all the measures being taken to mitigate the pandemic, and I just wanted to highlight a few of those examples. These are things that have just happened in the last few weeks to give everyone a sense of how things are still moving along in the cancer research enterprise.

So, one about which Im very excited is we enrolled our first patient on our CD33 CAR T trial. This is a trial for young adults and children with acute leukemia that has relapsed or refractory. And this is a first-in-man trial of a new CAR antigen and that reflects the work of Nirali Shah and collaborators at CHOP.

And thats all important, but what is particularly remarkable at this trial in my mind is that the cells were made at our new Frederick National Lab facilities. So, that cellular therapies facility is open for business now.

We have a vision of doing several types of highly personalized cancer therapy for patients at Frederick National Lab, and I think the cellular program is just the beginning of that. So, Id really like to congratulate Jim Doroshow and the Frederick National Lab team for getting this facility up and running so quickly.

The facility can make the CAR T cells there, and then ship them to a participating clinical trial site, in this case CHOP. And this technical advance is great news for kids and adults with leukemia, but I think well see it spread to other CAR T trials soon.

This is a paper that came out from the intramural program from [Division of Cancer Epidemiology and Genetics] about a week or two ago, also with collaborators at NIA and CDC, and this shows a very strong association of steps per day with all-cause mortality.

So, people who get 12,000 steps per day have a lower all-cause mortality than people who get 8,000 steps per day, who have a lower all-cause mortality than people who get 4,000 steps per day.

When Im sheltering in place during a pandemic, this issue is really key. Ive been trying to get out of the house to get my steps in, not just for my all-cause mortality, but for my mental health, and this great study was led by Chuck Matthews and others in DCEG.

This is a wonderful story 30 years in the making, 30 years of intramural research at the NIH about the use of selumetinib in NF1. It started with a fresh faced young geneticist named Francis Collins, who, while faculty at the University of Michigan, along with others, first discovered the gene NF1 that is mutated in this congenital pediatric cancer predisposition syndrome. And then people like Doug Lowy and others figured out what NF1 does from a biochemical standpoint and its role in Ras/MEK signaling.

And then a lot of studies, a number, over a decade of studies in the intramural program to try and address NF1 in patients. And those were largely led by Brigitte Widemann pictured here. And finally, after a lot of things that didnt work, recently the NCI and Brigitte have developed this therapy that is really a notable success. Its published recently in the New England Journal. This is not a cure for neurofibromatosis, but its incredibly meaningful for patients and vastly improves their quality of life. I really want to take my hat off to the people in the pediatric oncology grants who have developed this over so many years.

Theres just too much great science in the extramural community to mention it all and its so rapid and staggering in its output. I thought I would show one slide that I particularly liked, which is a story from my old friend Sean Morrisons lab showing this interesting relationship between metastasis and melanoma spread.

Metastasis is one of the great unsolved riddles of cancer research, and I think science like this that helps us understand the cellular basis of that process is really, really key, and is a good example of why basic research is what really moves the needle, in my opinion, for cancer patients over the long term.

And this is why Ive been such a fierce defender of the RPG pool my entire time, because it produces great basic science like this, and I believe someday were going to be able to prevent metastasis because of studies in this vein.

So, let me close now. I really wont sugarcoat our present circumstances. This epidemic is bad, and its going to continue to be bad for a while, especially the next few weeks. This period of waiting for some normalcy to return has made me think a lot about what it was like when I was a leukemia doctor.

In leukemia, in acute leukemia, you give patients a big bolus of chemotherapy, and then you wait four to six weeks for them to recover their bone marrow and go home. And induction chemotherapy, as many of you know, involves a lot of waiting and a lot of anxiety, hoping for a return to a more normal time.

And this period now reminds me a lot of waiting for bone marrow to return and the inpatient service while were waiting for this pandemic to abate. And in particular, Ive been thinking about a former patient from that time. He was an English professor who taught undergrads English literature, and hed gotten his induction chemotherapy, and was waiting in that hospital for his bone marrow to recover, so he could go home.

Now, a little-known fact is that I was an English major for about a month, as an undergraduate, before I realized how much writing an English major entails, and then I switched to become a math major. But Ive always loved literature, and Ive always taken the chance to learn from my patients. So, when I would come in every morning with my huge team of residents, medical students and pharmacists to round on this patient, we would always ask him for some great thought from English literature to summarize his day.

Original post:
Sharpless: NCI is fully operational, we have a moral obligation to help in the COVID-19 pandemic response - The Cancer Letter

Letters to the Editor: Tuesday, April 7, 2020 | Opinion – pentictonherald.ca

Theres no need to be obnoxious

Dear Editor:

During these difficult times, its very important for all of us to work together to maintain social distancing between ourselves and others.

The vast majority of people are making a real effort. However, there are individuals who are completely ignoring the advice we've been repeatedly given. These people are ignorant, inconsiderate and selfish and their actions endanger us all.

I like to ride the KVR trail regularly and every day I encounter a few individuals who flout the rules. Yesterday, after having encountered considerate and responsible people for most of my ride, I encountered my first obnoxious individual.

I was walking across the trestle as close to my side as I could and just when I was nearly across, two older women walked onto the trestle. I expected them to walk as close as they could on the opposite side. However, one of them walked right down the middle very close to me. I mentioned to her that she was not social distancing and she said that I was overreacting and continued walking down the middle of the trestle. In the next couple of minutes, I encountered two more people also in the middle of the trail and refusing to move. My comment received a similar reaction in each case.

I encountered more people today who refused to move to the side of the trail.

The most egregious example occurred in "the dip"northeast of Lakeview Cemetery. As I was about to go through, I noticed a young family at the lowest point of the dip. They were taking up more than half of the trail. The father was on my side of the trail. I rang my bell and asked him to give me room to get past and he refused. I mentioned social distancing and received the same answer as I had received from the other people who are not taking distancing seriously, but this time, it was spiced with profanity.

We encounter similar behaviour when we are walking and on our occasional shopping trips.

Its imperative that failure to socially distance legislation be passed so offenders can be fined and it needs to be enforced. These people don't need to be "educated. They know exactly what they're doing. Otherwise, this type of behaviour will continue and endanger us all.

Al Martens

Penticton

More praise for health-care stars

Dear Editor:

Last week, I experienced a severe pain crisis requiring an ambulance trip to the hospital for a three-day stay. I want to thank everyone who was there for me:

My daughter and son-in-law who came and unlocked the door for the ambulance crew;

The ambulance crew who so carefully removed me from the floor onto a stretcher;

The Emergency Room staff who cared for me, including doctors, nurses, lab technicians, my niece and other team members;

The porters who took me up to a bed on the second floor;

The nursing staff on the second floor;

The cleaning staff and the kitchen staff;

The phyiso and occupational therapy staff;

The doctors who took charge of my care;

My family doctor for his ongoing follow up;

My pharmacist who explained my medications and does home delivery;

Dr. Cleveland of the pain clinic who saw me as an urgent care case;

The records department that posted my report on MyHealthPortal.

And everyone else whom I have unintentionally overlooked.

With all these amazing people on staff at PRH, I am confident that we are as well prepared as we can be for whatever transpires in the COVID-19 pandemic.

Once again, thank you, thank you, thank you!

Fern Gibbard

Penticton

Walkers, dont forget your scoop

Dear Editor:

I love to walk as many people do. It seems that since the COVID-19 pandemic, there are a lot more people just going for walks which is such a great exercise, physically and mentally.

I am also finding there seems to be a lot more dog dropping on the sidewalks and walk ways. Please, if you are walking your pet, be sure you take along something to pick up after your pet. Leaving it on the sidewalk or walkway is a health hazard along with a mess for others to dodge or otherwise.

At this time, we are concerned about our environment and health so lets clean up after your animals so we all can enjoy our exercising. Lets stay fit and healthy

Hilda Bailey

Penticton

New information on making masks

Dear Editor:

Thursdays article on homemade masks suggests using furnace-filter material in homemade masks. Some internet research found that many furnace, vacuum, etc. filters contain glass fibers which could harm your lungs. Cutting of the material may release more particles.

3M Filtrete is a common furnace filter material. The following is a direct quote from their website: Our filters are designed to be used in HVAC systems, and the filter media has not been tested to be used as a face mask for respiratory protection. Altering any of our 3M Filtrete air filters is not recommended or supported by 3M or the Filtrete brand. Customer safety is our number one priority.

Bob Cole

Osoyoos

Appreciation for local columnist

Dear Editor:

It was a surprise to me not to find Jim Taylors Sharp Edges column in the Okanagan Weekend edition on March 21.

Consequently, I was so pleased to find his column Isolation causes its own problems, (Okanagan Weekend, March 28) until I was halfway through the article to learn that Jims wife had passed away two weeks earlier. Let me say, Jim, I am so sorry to hear of your wifes passing. You are not over-sensitive to the issue of isolation, as you questioned.You have so clearly articulated the need for human interaction; how basic it is to good health. Since I cant pat you on the back or shake your hand, just know that I along with your many readers and friends send condolences, not only to your but to all who have lost loved ones.

Your thoughtful, intelligent commentary in the paper is deeply valued and appreciated by so many. Will we re-assess our reactions to a crisis? Most assuredly! Will we slide back into old ways as if nothing had changed? Some might, but most wont.

As you wrote, We humans are social creatures. Perhaps this temporary isolation is a time for individual and group reflection. It is an opportunity to deeply consider our important relationship with family, friends, neighbours, health-care workers, community support workers and the planet we all inhabit.

For most, this is a time of going forward with greater respect and care for each other. Best wishes and keep writing!

Sandra Nicolson

Summerland

Situation in U.S. is much different

Dear Editor:

Response to Ted Wiltses suggestion of closing walkways in Penticton (Okanagan Weekend, letters, April 4).

The reason the U.S. is suggesting wearing masks is because they have done very little so far to control the pandemic. They need to show they are doing something.

Canada has been much more proactive and we are, for the most part, self-isolating and keeping our distance as suggested. The folks using the walkways are not coughing and sneezing on everyone as you imply, but are being cautious and are following the rules.

Perhaps you should personally visit the walkways and see for yourself before throwing out unnecessary and uneducated ideas. The Americans are not doing a good job of managing the pandemic, and I for one, do not listen to their unusual and unscientific suggestions, when our own federal, provincial, and civic governments are doing a great job in setting standards based on scientific knowledge.

I use the walkways to get my daily exercise and am very glad that we have these areas available to us, and we all know that following the guidelines will get us through this mess.

Paul Beattie

Penticton

Happy song list lacked Can-con

Dear Editor:

Re: The 25 happiest songs, by James Miller (Okanagan Weekend, April 6).

Good one, music is helping us all get through the crazy times. And heres some ideas for when you do your Canadian list: Share the Land (The Guess Who), Sunny Days (Lighthouse), Takin Care of Business (BTO), Something to Live For, (Barney Bentall), Life is a Highway (Tom Cochrane), Where Theres a Will (Sass Jordan), Hand in My Pocket (Alanis Morrisette), Go For Soda (Kim Mitchell), Fly at Night (Chilliwack), Old Dans Records (Gordon Lightfoot), Raised on Robbery (Joni Mitchell) OK, its kind of naughty ... but its Joni Summer of 69 (Bryan Adams), Heart of Gold (Neil Young), Up! (Shania Twain) and Havent Met You Yet, (Micheal Buble).

And now I will go back to doing the Caddyshack dance, a.k.a. the gopher shuffle.

Bob Vincent

Penticton

John Denver belongs on list

Dear Editor:

Good effort but a little too restrictive. Why not more diversity of beat and era? Scotch and Soda (Kingston Trio) never put on an LP Sunshine on my Shoulders (John Denver), Country Roads (John Denver, again), Its a Beautiful Morning (The Rascals) and This Ole Riverboat (The Back Porch Majority, Randy Sparks third folk group creation.)

Glenn Sinclair

Penticton

I think it was the Fourth of July

Dear Editor:

I enjoyed reading your list of happy songs and would like you to know you missed Saturday in the Park by Chicago from 1972. I remember it well when I cut grass for the neighbours letting it blast as I filled my gas tank on my little transistor radio.

Back then with less songs on demand, there was a certain thrill when your favourite song was played at unexpected moments suddenly cheering you up!

Paul Clark

Kelowna

What? Where were The Rascals?

Dear Editor:

Thank you James Miller for your list. Now I can add a few more up lifting songs to Spotify. If I can suggest, A Beautiful Morning by The Rascals could have been included. The song picks me up every time I hear it and never grows old.

By the way, my brother and I were paperboys back in the early 60s when we lived on Government Street. I proudly tell friends out in Naramata I was born in the old hospital. My wife and I are avid readers of The Herald.

Colin Ballance

Penticton

Nine happy songs he would include

Dear Editor:

1. You Are My Sunshine. written by Jimmie Davis in 1940. Sung by Gene Autry, The Singing Cowboy in a 1940s Oater. Gene sang it with a wide smile on his face. He had charisma and he expressed himself well. By dabbling in real estate, Gene ended up a multi-millionaire and owned the California (Los Angeles) Angels.

2. Oh, Happy Day by a Canadian group of Torontos St. Michaels Choir School, that called themselves The Four Lads. This deep-sounding song of sunny daisy over dark clouds of gray won me a prize for naming it as the best happy song out in the world of 1964.

3. Sunshine On My Shoulders by John Deutschendorf Jr., known professionally as John Denver, with his lilting voice that spreads the joy in his heart to all who hear him.

4. Hallelujah by Leonard Cohen. This immense repetitious song is of joy from the heart of him who gives. Leonard is repeating something he knows a lot about and that is the joy of being alive.

5. Let the Sunshine In by The Fifth Dimension. From Hair, this invite is to the positive side of life.

6. Sugar, Sugar by the Archies. Written by Jeff Bailey, it has an unforgettable snappy, wanting call of love to it. It was a four-week No. 1 single in 1969 that oozed happiness and kept in my memory for many years to come. What an upbeat song it was! Love, joy, happiness rolled up.

7. Dancing Queen by ABBA. Their only No. 1 hit in North America has that ABBA beat and performance that goes with it. Two gorgeous gals singing harmoniously about dancing and moving to the music with that ABBA beat. Inviting happiness in, is the message.

8. Africa by Toto brings back all the happy memories one has if one is ever on safari in the dark continent like I experienced in Uganda in 1971-72. Being surrounded by vibrant people and strange animal life and fauna is spewed out harmoniously and happily to all who will listen.

9. Aint No Sunshine When Shes Gone by Bill Withers is an upbeat, warm and memorable song about how good it was to love and to be loved by that someone special. True happiness!

Thank you for your list. Its great and I recognized most of them and looked up the ones I missed. Good for you. Well done.

Leo (Puckshot) Jacques

Read the rest here:
Letters to the Editor: Tuesday, April 7, 2020 | Opinion - pentictonherald.ca

Symptoms and causes of depression and its diagnosis and management – Nursing Times

Depression has a variety of symptoms and causes, and it can be diagnosed and treated in different ways. It is important that nurses can recognise patients presenting with depression. This article comes with a self-assessment enabling you to test your knowledge after reading it

Depression is a common condition. It presents differently in each person, but common symptoms include feelings of hopelessness, loss of interest in things previously enjoyed, and reduced motivation and energy. Diagnostic tools are available but, as they do not capture all the factors that affect depression, full clinical assessments are needed. Misdiagnosis is common. Causes of depression may vary but may relate to situational, genetic, biological, environmental or psychological factors. It often occurs alongside other mental health conditions or long-term physical conditions. Treatment options vary, depending on the severity of the episode, and a stepped-care approach is recommended. Depression can be recurrent, so treatment should focus on avoiding relapse.

Citation: Munro M, Milne R (2020) Symptoms and causes of depression, and its diagnosis and management. Nursing Times [online]; 116: 4, 18-22.

Authors: Mary Munro is lecturer, mental health nursing, Robert Gordon University Aberdeen and community mental health nurse (substance misuse), Royal Cornhill Hospital Aberdeen; Rosa Milne is community mental health nurse (adult services), Royal Cornhill Hospital Aberdeen.

Depression is a major public health issue in the UK and worldwide (Norman and Ryrie, 2018). It is estimated to affect 264 million people globally (GBD 2017 Disease and Injury Incidence and Prevalence Collaborators, 2018), and defined by the World Health Organization (2020) as a leading cause of disability worldwide and a major contributor to the overall burden of disease. WHO (2020) defines depression as low mood and loss of enjoyment in things that were previously enjoyed.

The human experience involves periods of low mood or difficulty, but for most people these feelings pass. The difference between a low mood and depression is when an individuals feelings consistently interfere with their daily life over a minimum period of two weeks (Norman and Ryrie, 2018). An episode of depression can vary in duration from weeks to years, but normally lasts for a minimum of several weeks (Mind, 2017).

For any diagnosis of depression, and ideally before treatment options are explored, the severity of an individuals depression should be ascertained; this is indicated by their symptoms. Symptoms may vary between individuals but, generally, they will encompass feelings of sadness and hopelessness (Lotfaliany et al, 2019). Norman and Ryrie (2018) have said the signs and symptoms of depression can be split into two categories: how an individual feels and how these feelings affect their behaviour.

Common feelings associated with depression include:

The detrimental effect these feelings have on how an individual behaves in their daily life means that behavioural symptoms often include a lack of motivation in personal care, work and relationships. Most people present with a variety of signs and symptoms; the most common are listed in Box 1 (Norman and Ryrie, 2018).

Box 1. Common signs and symptoms of depression

Two main classification system manuals are used to diagnose depression:

Both manuals categorise depression into three main categories mild, moderate and severe depending on the number of symptoms (Table 1), their duration and frequency.Mild depression. The DSM-5 defines mild depression as:

Symptoms must be evident but not presenting to an intense degree. There may be some difficulty continuing with ordinary work and social activities, but they will not stop completely.

Moderate depression. Christensen et al (2019) define moderate depression as:

Symptoms are present to a marked degree, and there is difficulty continuing with daily activities.

Severe depression. DSM-5 categorises severe depression as:

Health professionals can use a variety of tools to help with accurate and robust diagnosis of depression (Nabbe et al, 2018). However, NICE (2009) identified that a range of biological, psychological and social factors can have a significant impact on depression and are not wholly captured by diagnostic systems. It is, therefore, vital to consider the individuals personal history and family history of depression during a diagnostic assessment (NICE, 2009).

The Whooley questions for depression screening (Box 2) form a commonly used depression diagnostic tool. However, findings have suggested the tool alone cannot determine whether a person has depression; if they answer yes to one or both questions, a full clinical assessment is needed (Bosanquet et al, 2015). The assessment can be carried out by a GP or, if the patient presents in secondary care, an assessing nurse or doctor who is competent to perform a mental health assessment. The assessment must evaluate the persons mental state and accompanying functional, interpersonal and social difficulties (NICE, 2009).

Box 2. Whooley questions for depression screening

Yes to one or both questions = positive test (requires further evaluation)

No to both questions = negative test (individual does not have depression)

Source: Whooley et al (1997)

Nurses work at the forefront of patient interaction and care. It is, therefore, essential that they understand depression, along with its signs, symptoms and clinical, social and economic impacts to be able to provide effective person-centred care. Nurses from all fields can learn to recognise depression and ensure further assessment and interventions are offered.

Misdiagnosis of depression is common (Bostwick, 2012) because several illnesses have similar symptoms; for example, hyperthyroidism symptoms include low mood, reduced attention span and fatigue.

Depression is underdiagnosed in older adults (Rodda et al, 2011) and can be misdiagnosed as dementia due to the similarity in some symptoms, such as increased social isolation and mood changes. An assessment tool such as the General Practitioner Assessment Of Cognitionmay be required to differentiate between symptoms of depression and dementia.

Depression is a complex condition, and its causes are not fully understood. Genetics, biology, environment and psychological factors may play a role, and it can affect people of any age, race and socioeconomic status. Why people experience depression varies, so it is important to treat each person individually and understand their symptoms and behaviours by getting to know them dont look at the diagnosis of depression alone, as the cause will be personal to individual (Norman and Ryrie, 2018).

In the Adult Psychiatric Morbidity Survey undertaken in England in 2014, 3.3% of respondents reported that they were experiencing depression (McManus et al, 2016), while in Scotland 20% of the adult population experienced one or more symptom of depression in 2014/15 (Mental Health Foundation, 2016).

Although the exact reasons why depression manifests are unclear, there are some theories to help our understanding. Almost all community epidemiological studies find that gender, age and marital status are associated with depression. Kessler and Bromet (2013) have suggested that adult women are at almost double the risk of severe depression compared with men and a study by Van de Velde et al (2010) identified that women represented statistically higher rates of severe depression in 15 of the 18 countries they studied. Kessler and Bromet (2013) suggested people who are separated or divorced have significantly higher rates of severe depression, compared with those who are married.

Some studies suggest that genetics can influence the risk of developing depression for example, Elwood et al (2019) have found that some genes may play a key role in developing recurrent depression. However, it must be noted that there is no one gene linked to depression.

Studies have shown that lifestyle choices such as a lack of exercise, being underweight or overweight and having fewer social relationships can increase the risk of developing depressive symptoms (Esiwe et al, 2015). The use of legal and illegal drugs may also be a way of coping for some individuals, and has been linked to a greater risk of developing depression as well as other mental health conditions (Esiwe et al, 2015).

Ongoing research suggests that people who have experienced adverse childhood events, trauma or abuse have increased symptoms of depression compared with the general population (Bond, 2019). Depression has also been found to be more prevalent in people with a lower socio-economic status and a lower subjective social status (Hoebel et al, 2017). There is also evidence suggesting an association between social deprivation and depression: Fiske et al (2009) found that people in areas of great deprivation are four times more likely than the general population to experience depressive symptoms.

A number of studies have highlighted the link between depression and long-term physical health conditions, including:

The life expectancy of people who are diagnosed with severe depression is 10years lower than that of the general population; one reason for this is the higher suicide rate in this group, but it is also because depression elevates the risk of the onset, persistence and severity of a wide range of physical disorders (Norman and Ryrie, 2018). Long-term physical conditions can also cause or exacerbate depressive symptoms (NICE, 2009). This comorbidity has been attributed to:

These findings emphasise the importance of careful psychological assessment and treatment of people with a long-term physical condition, even in the critical stages of a disease. Nurses in all fields should consider the mental health of people in their care.

Depression can exist comorbidly with other mental health conditions, including substance use disorders (Blanco et al, 2013). Kellner et al (2012) said this was partly because people with a substance use disorder commonly face stigmatisation, marginalisation and financial insecurity, which can cause depressive symptoms. People with a substance use disorder who have a diagnosis of depression are at a higher risk of death by overdose than other substance users (Pabayo et al, 2013). Kellner et al (2012) identified that 50% of people with a substance use disorder reported symptoms of severe depression but were not receiving any treatment for it.

Another common comorbidity of depression is anxiety disorder (Hranov, 2007). Having both anxiety and depression has been found to increase the severity and number of symptoms of each condition, resulting in greater impairment (Hofmeijer-Sevink et al, 2012). Some of the symptoms of anxiety and depression also overlap, for example overthinking, avoidance and sleep disturbance (WHO, 2020). The high rate of comorbidity of anxiety and depression suggests we should consider the occurrence of one disorder as a pre-disposing factor for developing the other (Cameron, 2007).

NICE (2009) recommended a stepped-care approach to treat depression, using a framework that lists the most-effective interventions (Table2). In stepped care, the least-intrusive, most-effective intervention is provided first; if a person does not benefit from it, or declines it, they should be offered an appropriate intervention from the next step.

Cognitive behavioural therapy, behavioural activation methods, self-help approaches, interpersonal therapy and counselling have all proved effective psychological interventions for depression (Ekers and Webster, 2012). Both technology-assisted and face-to-face therapy have been found to be effective (Zhang et al, 2019).

Electroconvulsive therapy can be used for severe depression; despite controversy about the treatment, due to misconceptions or unfamiliarity, it is acknowledged as one of the most-effective treatments for severe mood disorders (Kellner et al, 2012).

Newer treatments are being developed for treatment-resistant depression, such as esketamine given by infusion (Bozymski et al, 2019). Most first-line antidepressants take 4-6weeks to achieve full effect; the response time for esketamine is as short as 2-24hours post-administration in clinical trials (Bozymski et al, 2019). Although esketamine could be a promising option for treatment-resistant depression, its disadvantages include its cost, the time commitment required to attend an infusion clinic and its unpleasant side-effects. According to the British National Formulary these include arrythmias, dizziness, hypersalivation, nausea, vomiting, respiratory issues, sleep disorders and vision problems.

Treatment and support for depression can come from many health professionals in primary or secondary care, depending on the severity of symptoms. Mental health nurses, GPs, occupational therapists, psychologists and psychiatrists can all provide evidence-based interventions. Core interventions for nurses working with people with depression include:

NICEs (2009) guidance stated that when working with people who have depression, best practice means:

Stigma is a significant issue in mental health: it lowers peoples self-esteem, makes symptoms more severe and limits help-seeking behaviours (Sastre et al, 2019). Nurses should be aware of the potential for self-stigmatisation in people with depression. Forming an effective therapeutic alliance has been shown to improve clinical outcomes in people with depression (Arnow et al, 2013) and reduce negative self-perception (Porr et al, 2012).

Community and third-sector support is also often available. This can include:

These have been shown to improve symptoms (Rosenbaum et al, 2014; Cruwys et al, 2013; Sanchez-Villegas and Martnez-Gonzlez, 2013; Pfeiffer et al, 2011).

A key part of recovering from a mental health condition is patient choice; people with depression may benefit from a multifaceted, holistic approach to treatment (Loos et al, 2017).

Depression is common and often chronic and recurrent (Uher and Pavlova, 2016). Its symptoms and outcomes are marked by persistent suffering, poor overall health and negative effects on several areas of life, including psychosocial, academic and work life (de Zwart et al, 2018). One study found that fewer than a third of patients recovered and remained well in the 18months after an episode of depression (Mulder, 2015). This suggests treatment needs to focus on maintaining wellness and preventing relapse.

To help prevent relapse, it is helpful to use the recovery model, a holistic, person-centred approach to mental health care that is becoming the standard model. It is based on two simple premises:

A significant part of sustained recovery from depression is being able to avoid or cope with relapse risk factors (Jumnoodoo et al, 2017). Recovery can mean a person staying in control of their life and living in a way that is meaningful to them, rather than returning to the level of functioning they experienced before depression (Jacob, 2015). Although depression is a chronic condition that can recur throughout someones life (Uher and Pavlova, 2016), this does not have to mean a state of consistent suffering and powerlessness but, instead, a journey that includes setbacks and successes (Scottish Recovery Network, NHS Education for Scotland, 2007).

Modern-day living and its pressures have been linked to a rise in depressive symptoms and prevalence of depressive disorders (Hidaka, 2012; Walsh, 2011). Although psycho-education, medication and psychological approaches have been shown to be effective at treating depression (NICE, 2009), people can take several lifestyle approaches to maintain good mental health. These include:

Nurses are well-placed to advise patients on these.

This article has provided a general overview of depression, its treatment, outcomes and significance when providing nursing care and assessment. As nurses in all settings and specialties work at the forefront of patient interaction and care, a knowledge of depression, its signs and symptoms, and its potential implications for patients is essential to provide person-centred care. Nurses from all fields can learn to recognise depression in their patients and ensure further assessment and interventions can be offered.

References

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Bond P (2019) Falling through the net: unrecognised trauma. Healthcare Counselling and Psychotherapy Journal; 19: 1, 8-13.

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Excerpt from:
Symptoms and causes of depression and its diagnosis and management - Nursing Times

Twelve Women Who Have Shaped The History of the BioHealth Capital Region – BioBuzz

The BioHealth Capital Region (BHCR) and its life science ecosystem have a rich and deep history of pioneering scientific innovation, research, development, and commercialization. The regions history has been written by life science anchor companies, scientific research universities, government research organizations, rich startup culture, and serial entrepreneurs, all of whom have played critical roles in transforming the BHCR into one of the most innovative and productive biocluster in the world.

Contributions to the BHCRs legacy of life science achievement have emerged from all staffing levels, various labs, countless executive teams, numerous entrepreneurs and biohub support organizations. Contributions have arisen from an intricate tapestry of backgrounds and cultures.

Women, in particular, have had a strong hand in shaping the history of the BHCR. In celebration of Womens History Month, were taking a closer look at the achievements of female life science leaders that have laid the groundwork for the next generation of women trailblazers in the BHCR and made the region what it is today.

Dr. Fraser is one of the most influential figures in BHCR history. In 1995, she was the first to map the complete genetic code of a free-living organism while at the Institute for Genomic Research (TIGR) in Rockville, Maryland. It was there that the automation of the DNA sequencing process made the idea of large-scale sequencing efforts tangible. As President and Director of TIGR, Fraser and her team gained worldwide public notoriety for its involvement in the Human Genome Project, which was completed in 2000 with the presentation of a working draft of the fully sequenced human genome.

As a leader, Fraser provided her researchers with the infrastructure to collaborate and apply multi-disciplinary team science and empowered them to think big. She is also most importantly known for how she challenged her team to ask the right questions, which is the root of scientific progress and success.

Her work at TIGR and as part of the Human Genome Project are foundational events in the regions history, as it marked the BHCR as the epicenter of genomic research and helped spark the regions biotech boom. In fact, it was a controversial partnership with TIGR that gave Human Genome Sciences(HGSi) the first opportunity to utilize any sequences emerging from TIGR labs. The mass of genetic information and sequences, especially that associated with diseases, that HGSi acquired catapulted them into biotech history and an important anchor company within the region.

Dr. Fraser is widely viewed as a pioneer and global leader in genomic medicine; she has published approximately 320 scientific publications and edited three books; she is also one of the most widely cited microbiology experts in the world. She founded the Institute for Genome Sciences at the University of Maryland in 1997. The institute currently holds 25 percent of the funding thats been awarded by the Human Microbiome Project and has been referred to as The Big House in genetics.

Dr. Judy Britz is yet another female life science pioneer that put the BHCR on the map. While working as a research scientist at Electro-Nucleonics Inc., Dr. Britz developed one of the first licensed blood screening tests for HIV, and launching a storied career that has spanned approximately 25 years. She is also a serial entrepreneur that has successfully raised $50M in capital and served as the top executive for two highly successful Maryland-located companies.

Dr. Britz was the first woman to lead the states biotech initiative as the first announced Executive Director of the Maryland Biotech Center. The center was launched under the Maryland Department of Commerce to deploy a strategic life science economic development plan under Governor Martin OMalleys $1.3B, 2020 Vision and to be a one-stop-shop and information center to promote and support biotechnology innovation and entrepreneurship in Maryland.

Judy was the first woman to lead Marylands life sciences initiative, bringing industry experience and perspective to the states economic development activities, a focus still maintained under Governor Hogans leadership today, shared Judy Costello, Managing Director, Economic Development BioHealth Innovation, Inc., who served as Deputy Director under Dr. Britz.

Much of the work done by Dr. Britz and her team laid the foundation and seeded the commercialization efforts that have blossomed into the thriving #4 Biotech Hub that we have today.

GeneDx was founded by Dr. Bale and Dr. John Compton in 2000. The company recently celebrated its 20th anniversary. Since its founding, GeneDx has become a global leader in genomics and patient testing. Under her leadership, the Gaithersburg, Maryland company has played an important role in the history of genetic sequencing and the rise of the BHCR as a global biohealth cluster.

GeneDx was the very first company to commercially offer NGS (Next Generation Sequencing) testing in a CLIA (Clinical Laboratory Improvement Amendments) lab and has been at the leading edge of genetic sequencing and testing for two decades. The companys whole exome sequencing program and comprehensive testing capabilities are world-renowned.

Prior to launching GeneDx, Dr. Bale spent 16 years at NIH, the last nine as Head of the Genetic Studies Section in the Laboratory of Skin Biology. She has been a pioneer during her storied career, publishing over 140 papers, chapters and books in the field. Her 35-year career includes deep experience in clinical, cytogenetic, and molecular genetics research.

Prior to being named CEO and Chair of the Board of Sequella in 1999, Dr. Nacy was the Chief Science Officer and an Executive VP at EntreMed, Inc. EntreMed was one of the most influential BHCR companies in the 1990s. EntreMed, MedImmune, Human Genome Sciences and Celera Genomics all played critical roles in creating the globally recognized, top biocluster that the BHCR has become.

After earning her Ph.D. in biology/microbiology from Catholic University, Nacy did her postdoc work at the Walter Reed Army Institute of Research in the Department of Rickettsial Diseases; her postdoc performance earned a full-time position at Walter Reed that started a 17-year career at the institute. After a highly successful run, Nacy left Walter Reed to join EntreMed.

Today, Dr. Nacy leads Rockville, Marylands Sequella, a clinical-stage pharmaceutical company focused on developing better antibiotics to fight drug-resistant bacterial, fungal and parasitic infections. Sequellas pipeline of small molecule infectious disease treatments have the potential to improve the treatment and outcomes for the over 3 billion people worldwide that are impacted by increasingly drug-resistant infectious diseases.

Emmes Corporation is the largest woman-led organization in the BHCR and is headed by Dr. Lindblad, who started her career at Emmes in 1982 as a biostatistician. She has been with Emmes for nearly 40 years, ascending to become VP in 1992, Executive VP in 2006 and ultimately the companys CEO in late summer of 2013.

Dr. Lindblad has published more than 100 publications and presentations has served as a reviewer of grant and contract applications for the National Institutes of Health (NIH) and has chaired or served on Safety and Data Monitoring Committees across multiple disease areas. Emmes is a life science anchor company for the BHCR, employing more than 600 staff globally with its headquarters in Rockville, Maryland.

Under Kings leadership, GlycoMimetics (GMI), an oncology-focused biotech, went public, secured an exclusive global licensing agreement with Pfizer and was instrumental in raising significant amounts of capital for the company. She was also the first woman Chair of Biotechnology Innovation Associations (BIO, 2013-14), where she still plays an active role on BIOs Executive Committee.

A graduate of Dartmouth College and Harvard Business School, King has had a celebrated career in both biopharma and finance. Prior to becoming CEO of GMI, King served as an Executive in Residence for New Enterprise Associates (NEA), one of the leading venture capital firms in the U.S. She has also held the position of Senior Vice President of Novartis-Corporation. King joined Novartis after a remarkable ten year run with Genetic Therapy, Inc. where she was named CEO after helping Genetic Therapy navigate the organization through various growth stages, including the companys sale to Novartis. King was named the Maryland Tech Councils Executive of the Year in 2013, the Top 10 Women in Biotech by FierceBio and has served on multiple boards across her career.

Dr. Connolly has had a pioneering career in the life sciences. She was the very first woman to graduate from Johns Hopkins Universitys Biomedical Engineering Doctoral Program in 1980. She was also a member of the first female undergraduate class entering Stevens Institute of Technology in 1971.

For decades, Dr. Connolly tirelessly worked to build up what is now known as the BHCR. In 1997, shortly before the region gained wider recognition as a biotech hub, she was the first person to be designated the state of Marylands biotechnology representative. Dr. Connollys career has spanned academia, government, and industry, including co-founding a startup and working as the Business Development Director for EntreMed, Inc., an original BHCR anchor company. She is the former Director of Maryland Industrial Partnerships Program (MIPS) and was inducted into the College of Fellows by the American Institute for Medical and Biological Engineering (AIMBE) in 2013.

Dr. Kirschstein played an enormous role in shaping the BHCR as NIH Deputy Director from 1993 to 1999 during the regions early formative years. She also served as Acting Director of NIH in 1993 and from 2000 to 2002. A pathologist by training, she received her medical degree from Tulane University in 1951 and went on to a long, successful career at the Division of Biologics Standards that lasted from 1957 to 1972.

While at the Division of Biologics Standards, Dr. Kirschstein played an important role in testing the safety of viral vaccines and helped select the Sabin polio vaccine for public use. She eventually ascended to Deputy Director of the group in 1972 and was later appointed the Deputy Associate Commissioner for Science at the FDA. In 1974 she became the Director of the National Institute of Medical Sciences at NIH and served in that role for 19 years.

Her awards and accolades are too numerous to list, but one notable honor came in 2000 when she received the Albert B. Sabin Heroes of Science Award from the Americans for Medical Progress Education Foundation.

Lastly, we want to recognize four additional women for their contributions to launching an organization that has impacted thousands of women by promoting careers, leadership, and entrepreneurship for women in the life sciences Women In Bio.

Women In Bio (WIB), one of the most important and influential support organizations for women in the life sciences, was founded in 2002 to help women entrepreneurs and executives in the Baltimore-Washington-Northern Virginia area build successful bioscience-related businesses. WIB started as a BHCR organization but has expanded its footprint to 13 chapters across the U.S. with 225 volunteer leaders and 2,600 members. The non-profit group has created a forum for female life science entrepreneurs and executives based on its core philosophy of women helping women.

WIB founders are Anne Mathias, a local venture capitalist and current Senior Strategist with Vanguard;

Elizabeth Gray, co-founder of Gabriel Pharma and current Partner at Willkie Farr & Gallagher LLP;

Robbie Melton, former Director of Entrepreneurial Innovation at TEDCO and current Director of Kauai County, Hawaiis Office of Economic Development;

and Cynthia W. Hu, COO, and General Counsel at CASI Pharmaceuticals.

In conclusion, we can not fairly capture the true history of life science and the BioHealth Capital Region without giving special recognition to Henrietta Lacks. In 1951 a Johns Hopkins researcher created the first immortal human cell line from cervical cancer cells taken from Lacks. That cell line, known as HeLa, is the oldest and most commonly used human cell line which was essential in developing the polio vaccine and has been used in scientific landmarks such as cloning, gene mapping and in vitro fertilization.

Though she was a black tobacco farmer from southern Virginia, her impact on science and medicine is unquestionable. She never knew that the Doctor took a piece of her tumor that would be used by scientists who had been trying to grow tissues in culture for decades without success. For some reason, that is still unknown, but her cells never died and the first immortal human cell line was born.

Thank you to all of the women who have been so influential in shaping the field of science, the industry of biotechnology and the BioHealth Capital Region.

Steve has over 20 years experience in copywriting, developing brand messaging and creating marketing strategies across a wide range of industries, including the biopharmaceutical, senior living, commercial real estate, IT and renewable energy sectors, among others. He is currently the Principal/Owner of StoryCore, a Frederick, Maryland-based content creation and execution consultancy focused on telling the unique stories of Maryland organizations.

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Twelve Women Who Have Shaped The History of the BioHealth Capital Region - BioBuzz

Coronavirus weekend update: Plans outlined to prepare hospitals for surge in patients – Mountain View Voice

Santa Clara County is working with local hospitals to prepare for an expected surge in coronavirus patients, county Board of Supervisors President Cindy Chavez and Santa Clara Valley Medical Center CEO Paul Lorenz said at a press conference on Sunday.

Lorenz said there are approximately 2,500 hospital beds in the county. Roughly 400 of the beds are dedicated to pediatric care and 350 are for critical care, 75% to 80% of which are currently occupied. Approximately 290 additional beds can be converted to an "ICU level of care," he said.

"If in fact the demand goes beyond our capacity, we are working with the county emergency operations center to come up with a communitywide search plan," he said. "That plan would include looking at all 2,100 adult beds that we can equip and staff for critically ill patients."

Lorenz added that "less acute patients" could then be taken to alternative facilities in the county to free up room at hospitals.

The county is also looking to hire more health care workers and is bringing retired employees back into the workforce. The county can reach out to the state and federal governments for additional staff should that be necessary, Lorenz said.

"We need to have the surge capacity in place as quickly as possible," he said. "We are moving as rapidly as we can. ... All of the hospitals in this county have prepared their own surge capacity plans, and that allows those facilities to ramp up their own facilities beyond what they're currently staffed at.

"I think the most important variable in all of this is to maintain our health care workforce and to grow that workforce ... and the ability for us to equip those hospital beds with ventilators and other necessary equipment. We are also moving very rapidly with the county EOC, the state and the federal government to make sure we have those items in place as quickly as possible."

He said the community has been "really helpful" in following the directions of local health officials, adding that local emergency rooms are now seeing a "much lower volume." Anyone with symptoms of COVID-19 is being asked to call their health care provider or 211 before going to urgent care or an emergency room.

"We were not expecting to have the results so quickly of the emergency rooms not being crowded because people are actually taking those steps, and that's really critical," Chavez said. "We want to make sure we have beds for people who are in the highest need."

Chavez provided another piece of good news: Community members have donated thousands of masks, gowns and other personal protective equipment for health care workers amid a national shortage of such items. The Valley Medical Center Foundation is continuing to collect monetary donations online and protective equipment, which can be dropped off beginning at 8 a.m. Monday, March 23, at the foundation's office on the Santa Clara Valley Medical Center campus, 2400 Clove Drive in San Jose.

Masks and gloves that aren't hospital grade are also needed for local food bank workers, she noted.

Chavez also encouraged those who are healthy and want to volunteer to deliver meals to sign up at siliconvalleystrong.org.

Access a recording of the press conference here.

Santa Clara County

Santa Clara County reported two more deaths and 39 new infections as a result of the coronavirus on Sunday afternoon, bringing the total number of cases to 302.

Chavez said in a press conference Sunday that the ninth and 10th recorded deaths in the county were women in their 60s and 40s, respectively. Both women died Saturday, March 21. The woman in her 40s was hospitalized Monday, March 16, according to the county. Further information was not provided.

Officials also announced in a press release Sunday that Santa Clara County Director of Communications and Public Affairs Maria Leticia Gmez has tested positive for COVID-19.

She became ill on March 13 and received her positive test result on Sunday, March 22.

Gmez agreed to share her health status publicly, according to the press release. She has been isolated at home since March 13.

"The county has instructed all employees, including those who have been in contact with Ms. Gmez, that they should not go to work if they show any symptoms of illness," the county said. "We are also notifying all members of the county workforce with whom Ms. Gmez may have had contact while contagious that they may have been exposed."

Of Santa Clara County's COVID-19 cases, 108 people are hospitalized; 77 are presumed to have been community transmitted; 75 are close contacts of known cases; 22 are associated with international travel; and 10 people have died, according to the county's public health department.

On Saturday, the county reported 67 new cases of coronavirus, which marked the biggest jump in cases in one day for the county.

"This increased case count is not unexpected given community transmission, an increase in provider reporting, and growing testing capacity through the commercial market," according to a county press release.

San Mateo County

As of Sunday morning, March 22, San Mateo County announced seven new COVID-19 cases, bringing its county total to 117, and one death.

Parking restrictions near Windy Hill Preserve

Portola Valley Town Manager Jeremy Dennis issued an emergency order on Sunday that prohibits parking adjacent to the entrances to Windy Hill Preserve's trails on Portola and Alpine roads and Willowbrook Drive, according to a Sunday afternoon email sent out to residents by Mayor Jeff Aalfs.

"Our experiences (including reports from many of you) over the last two days at Windy Hill indicate that not only are some of the trails incompatible with social distancing, the use of our streets for parking and trail entry is creating unsafe conditions as well," Aalfs wrote.

The order will be enforced beginning Monday, March 23, "until the County Order is lifted," he said. There will be increased signage in the affected areas.

Windy Hill, a Midpeninsula Regional Open Space District preserve, is among several local spots that have seen an uptick in visitors in recent days. The National Park Service announced in a tweet Saturday night that it would close multiple gates at Point Reyes National Seashore beginning Sunday, March 22, "after unprecedented visitation."

The open space district reaffirmed Friday, March 20, that its preserves and trails are open to the public with new health and safety measures in place, including: restrooms are closed; areas with high use will be intermittently closed without notice to promote safe social distancing; group gathering areas are closed; and group activities are suspended.

Aalfs noted in his email that town staff "has been in touch with San Mateo and Santa Clara County officials, MROSD officials, the Sheriff's Office, and others in discussion about the use of open space facilities during the current shelter in place crisis," but did not specify whether further measures are being considered at this time.

SAFE farmers market

For three weeks beginning Thursday, March 26, the SAFE (Sanitary Allocation of Food Essentials) Portola Valley Farmers Market will operate from 2 to 6 p.m. at the site of the usual Thursday farmers market, 765 Portola Road, according to an email from the town Sunday.

The market will be pre-order only with drive-thru pickup. Food will be prepacked, and households will be limited to five bags per order. The deadline for all orders will be 7 p.m. the Wednesday before the market, and products for the following week's market will become available online at noon every Friday.

The market will also offer special delivery for residents of the Sequoias retirement community and those in vulnerable populations.

For more information or to pre-order, visit the SAFE Portola Valley Market website.

Menlo Park-based lab to process coronavirus tests from new Hayward center

A partnership with a Menlo Park genetics laboratory firm will allow Hayward to open a dedicated center offering free COVID-19 coronavirus testing on Monday, March 23.

The COVID-19 testing center at the city's fire station at 28270 Huntwood Ave. can handle up to 370 tests a day, "But we don't expect it to get that high," said city spokesman Chuck Finnie.

Tests are intended for those displaying symptoms, first responders, and health care workers with recent suspected exposures to the novel coronavirus.

The intent is "to take pressure off hospital emergency rooms, provide quicker answers for recently exposed first responders and health care workers, and to enhance the region's capacity to suppress new transmissions through isolation after testing," the city said in an announcement Sunday.

"We don't want the wondering and the worried to come they need to stay home," Finnie said. "We want sick people to come."

He added, "It's not a test people are going to want to take unless they have to. It's not pleasant."

The test involves swabbing of nasal cavities and the back of the throat.

Hayward Fire Department firefighter-paramedics will staff the center, with assistance from ambulance company emergency-medical technicians.

"No referral from a medical doctor is required to be screened," the city said.

The center will operate from 9 a.m. to 6 p.m. daily and is free and open to "anyone regardless of where they live or immigration status," according to the announcement.

"We know it's going to be chaotic on the first day," Finnie said.

People will first undergo a two-part screening for illness, which includes fever, cough and/or shortness of breath, and/or other respiratory symptoms.

At an initial drive-up station, people will be asked about symptoms, then either be cleared to leave or sent to a walk-up tent to be screened for illness.

The city has appropriated funding for the center with the hope of reimbursement from county and state public health agencies.

The center is made possible through a city partnership with Menlo Park-based Avellino Lab USA Inc., a company that specializes in "gene therapy and molecular diagnostics with a focus in precision medicine for eye care."

The laboratory will analyze the tests and "Results can be available in as little as six hours or the next day in most cases."

Finnie said Avellino is a civic-minded company that is supplying the tests "at a very, very good price" and is also looking for similar partnerships with other jurisdictions to open additional centers.

He said officials from Fremont were assessing the Hayward center on Sunday.

Menlo fire begins pandemic response unit

The Menlo Park Fire Protection District now has a Pandemic Emergency Response Unit staffed by a two-person team. The unit is tasked with taking calls of suspected COVID-19 cases, according to a press release issued Saturday.

The district recently received seven calls of suspected COVID-19 in one day and expects to see that number go up.

Staff assigned to the unit will utilize the "highest level of Emergency Medical Services" and personal protective equipment. The district said they will aim to minimize contact with whoever may have COVID-19 while on a call to decrease possible exposure to the disease.

They will also be responsible for decontaminating each scene they visit and fire apparatus used on the call to prevent traces of the virus on equipment, clothing and/or the apparatus as outlined by district guidelines.

"We believe that by raising the bar on our personal protective clothing and by putting this new special response unit in place, we can slow or help to hopefully more effectively stop its spread," Chief Harold Schapelhouman said in the press release.

Some fire district personnel have volunteered to serve on the unit, he said.

"The number of our off-duty firefighters grew again today, as yet another Menlo Park Firefighter, the seventh, was home sick and scheduled for testing.

"At some point, we know one of our firefighters will contract COVID-19," Schapelhouman added, "most are not in the risk categories and all are extremely healthy and fit based upon the daily expectations of our profession, but our collective goal is to delay, or stop, spread for as long as possible."

Increasing health care capacity

To create more space at hospitals, Santa Clara County has teamed up with the U.S. Office of Public Health Preparedness and Response to establish a temporary Federal Medical Station at the Santa Clara Convention Center to accommodate up to 250 people, according to a statement issued Saturday. The station will be managed by the federal office to serve patients in need of short-term, subacute care and do not have COVID-19. It will be equipped with beds, supplies and medicines, according to the county.

The station, being developed with federal, state and local agencies, is expected to help make more acute hospital beds available.

Chavez said Sunday that the county is considering other sites besides the convention center for coronavirus response efforts but didn't offer any specific details.

The state can also increase capacity at clinics, mobile health care units and adult day care facilities as part of its COVID-19 response under an executive order issued by Gov. Gavin Newsom on Saturday. In addition, local governments are allowed to work with retired employees in addressing the public health crisis. The order also "reinforces the importance of the delivery of food, medicine and emergency supplies," according to a press release from the governor's office. To read a copy of the order, visit gov.ca.gov.

Reporting violations and fraud

On Saturday, Santa Clara County announced an updated resource for the public to report nonessential businesses they see operating in violation of the shelter-at-home order, which was issued on Tuesday and will last through April 7.

The public can notify the Santa Clara County District Attorney's Office of such breaches at a new phone number, 408-792-2300. Callers can leave a voicemail in English, Spanish and Vietnamese.

Additionally, the U.S. Department of Justice is encouraging people to report suspected fraud schemes related to the coronavirus by calling the National Center for Disaster Fraud hotline at 866-720-5721 or by sending an email to disaster@leo.gov. So far there have been reports of individuals and businesses selling fake cures for COVID-19 online; phishing emails from entities posing as the World Health Organization or the Centers for Disease Control and Prevention; malicious websites and apps that appear to share virus-related information to gain and lock access to devices until payment is received; and people seeking donations for illegitimate or nonexistent charities, according to the department.

Shelter at home orders

Last week started off with the announcement of a shelter-at-home order for most of the Bay Area and ended with a similar mandate extending throughout the state, actions taken in response to the growing coronavirus crisis.

On Monday, March 16, public health leaders from six Bay Area counties joined together to announce the shelter-at-home order for their respective jurisdictions. The measure limits the public to essential activities, such as health care operations; businesses that provide food, shelter and social services; and other necessities.

The state followed suit through its own order announced Thursday night by Gov. Gavin Newsom, who pointed to more than 1,030 confirmed cases and 18 deaths across California as factors in the decision.

Bay City News Service contributed to this report.

Find comprehensive coverage on the Midpeninsula's response to the new coronavirus by Palo Alto Online, the Mountain View Voice and the Almanac here.

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Coronavirus weekend update: Plans outlined to prepare hospitals for surge in patients - Mountain View Voice

Coronavirus: Hayward to open testing facility – East Bay Times

HAYWARD Officials said they plan to open a city fire station Monday as a site to test people for possible exposure to the COVID-19 virus.

In a statement Sunday, officials said the center at Hayward fire station No. 7, 28720 Huntwood Ave., will help to ease pressure at regional hospital emergency rooms seeking increased foot traffic.

The center will focus on testing first responders and health-care workers, but its biggest purpose is to reinforce the importance of post-testing isolation, city staff said.

Suppression, through isolation after testing, or SIT, as we call it, is an approach that has proven to be most effective in countries on the leading edge of this pandemic, Hayward Fire Department Chief Garrett Contreras said.

Hayward Fire paramedics, supported by ambulance emergency-medical technicians, will run the center everyday from 9 a.m. to 6 p.m., and it will be free to the public without city-resident, doctor-referral or immigration-status barriers.

Those who come will first be screened for illness, including specific symptoms such as fever, cough and shortness of breath, before receiving a nasal-cavity and throat-back swab. Test results are expected back within six hours, or next day at the latest, city staff said.

Menlo Park-based Avellino Lab USA, a gene-therapy and molecular-diagnostics firm, is partnering with the city to open the center, and plans to work with the city to open other testing sites around the Bay Area.

For more information, call its hotline at 510-583-4949 from 8 a.m. to 5 p.m. seven days a week, or visit the citys COVID-19 Web site at http://www.hayward-ca.gov/covid-19.

Contact George Kelly at 408-859-5180.

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Coronavirus: Hayward to open testing facility - East Bay Times

How CAR-T Immunotherapy Improves Quality of Life After Cancer Treatment – Healthline

Four years ago, Chuck Colletti, an athletic, gregarious family man from the suburbs of Pittsburgh who had never had any serious health issues, received a diagnosis of stage 4 follicular non-Hodgkins lymphoma.

Soon after, Colletti, 54, began a grueling 7-month chemotherapy regimen that succeeded in putting him in remission.

However, just 7 months after completing the chemotherapy, his cancer came back in a more aggressive form.

At that point, Colletti opted for another traditional regimen of treatment: 4 weeks of Rituxan, a monoclonal antibody.

It didnt work.

A bone marrow transplant was then considered, but Colletti told Healthline that because he had failed two treatments, he was now qualified to enroll in a clinical trial of a new, experimental immunotherapy his doctor mentioned.

It was called chimeric antigen receptor T-cell immunotherapy, better known now simply as CAR-T.

I had been reading about CAR-T. I knew about it and I told my doctor I definitely wanted to do it, Colletti said.

He subsequently enrolled in the Zuma-5 clinical trial of a CAR-T therapy called axicabtagene ciloleucel (Yescarta) from Kite, a Gilead company.

The trial was for the treatment of his lymphoma, which had transformed from follicular lymphoma into diffuse large B cell lymphoma (DLBCL).

The treatment, which came with some brief but serious side effects, has given him a lasting remission.

Im a very positive person. I know how lucky and blessed I am to receive CAR-T. There are many people trying to get it who still cant, said Colletti, who can now enjoy time again with his wife, Brandee, and their daughter, Gabriella.

Colletti is one of a number of people who report that CAR-T therapy not only conquered their cancer, but gave them a better quality of life afterward.

CAR-T involves collecting a persons T cells and genetically engineering them to produce special receptors on their surface that can recognize an antigen on targeted B cells.

The engineered T cells are then infused back into the person to find and attack cancer cells that have the targeted antigen on their surface.

In Collettis case, CAR-T not only gave him what appears to be a lasting remission, it changed his outlook on life.

Doing the CAR-T really made me much more aware of my need to help other people, he said. Not that Im not a compassionate person, but if you had told me 5 years ago that I would be doing public speaking or doing this interview with a journalist right now, well, I was always focused on doing things for work or with my family, just me and my family.

Colletti is now an advocate for his fellow lymphoma patients and for CAR-T, speaking about his cancer journey at Leukemia and Lymphoma Society events, podcasts, and conferences.

He says CAR-T isnt only saving peoples lives, its giving them an emotional boost and greater appreciation of life.

New research supports Collettis contention.

In the study published last month, participants with lymphoma whose disease was effectively treated with a CAR-T treatment called Kymriah reported that their treatment actually improved their quality of life and provided physical, social, and emotional benefits after their treatment was finished.

The study revealed marked improvement in a variety of self-reported quality of life issues.

This study confirms that if you have a long-term remission with CAR-T, your quality of life improves substantially, and in reality most patients return to normal life, said Dr. Constantine Tam, FRACP, FRCPA, a professor at the Peter MacCallum Cancer Centre at the Royal Melbourne Hospital and the University of Melbourne, and an expert in blood cancers.

Tam, an author of the study and member of the research team, told Healthline that the look at the quality of life of CAR-T patients was a companion study to the JULIET clinical trial of tisagenlecleucel (Kymriah) for people with relapsed or refractory DLBCL (r/r DLBCL).

The average age of the trial participants was 56 years and representative of the population with r/r DLBCL in the community. People up to 76 years were included and 23 percent were 65 or older.

The aim of the research, Tam said, was to document changes in quality of life for patients who receive this treatment, which ultimately turned out to be therapeutically effective and hence led to its licensing for r/r DLBCL.

Colletti didnt take part in the study, but he generally agrees with the findings.

I remember how scary it was when I first got that phone call and they told me I had stage 4 follicular non-Hodgkins lymphoma. I know what these patients were feeling, he said.

For me, when I help other people and talk about it, it helps me. I dont sit there in doom and gloom and think about it coming back. I move forward in a positive way. And CAR-T is responsible for that, he explained.

The CAR-T participants were asked questions about their treatment and about CAR-T by the same research team that worked on the JULIET trial in multiple cancer centers in the United States, Europe, Japan, and Australia.

The researchers queried participants on their quality of life using two tools.

One assessed physical, social, emotional, and functional well-being as well as disease- and treatment-related symptoms.

The other looked at the participants physical and social function, health perception, and mental health.

Data was collected before treatment and then again at months 3, 6, 12, and 18 following treatment, unless the participants discontinued participation in the study or their disease progressed.

Out of 108 evaluated participants, 57 achieved a complete or partial response to the treatment.

Baseline scores on participant-reported quality of life outcomes were similar between the total patient population and those who responded to the therapy, but responsive patients demonstrated continued improvement in quality of life measures over time.

Their most significant improvements were in areas of general health, vitality, physical function, and social function.

Many patients with this advanced level of disease become depressed and withdraw, but here patients reported improved functional status, physical capabilities, and ability to interact with people, Dr. Richard Maziarz, a professor of medicine at the Oregon Health & Science University School of Medicine and the studys lead author, said in a statement.

As we progress in our capacity to offer therapies to treat cancers, we have to ask: is it enough to just have our patients in remission or alive, or do we want them to be able to truly live again, and to re-enter society with full function?, he added.

For Colletti, there are a number of ways CAR-T therapy improves quality of life.

He says that for cancer patients, relying on the necessary poisons like chemotherapy and radiation is a double-edged sword.

We are killing the cancer but unfortunately also killing our healthy cells and organs, he said. Having the opportunity to receive CAR-T gives us a treatment that is not only less toxic than traditional regimens, but enables our body to battle this horrible disease from within.

Colletti says that having something inside your body that recognizes the disease cells and kills them is a welcome protocol.

I personally get up every morning thanking God for CAR-T. Knowing that my own body is now in control of my illness and the incredible power it has to keep killing my infected B cells is so reassuring, he said.

Basically having one CAR-T infusion and not months upon months of treatments is a blessing. I have always taken care of my body and now I really think my body is saying, It is time to take care of you, Colletti said.

He adds CAR-T gives him both a physical and emotional boost.

When you know you are an active part of the cure, it gives you such a confidence booster in continuing the fight, both mentally and physically, Colletti said.

It is also much more motivating to keep working on better lifestyle and health practices. When you take all of this and bundle it together, what you get is a more emotional, physical, and mental focus that is sometimes very hard to come by in traditional cancer battles. This is why I feel better about where I am now, he said.

As CAR-T progresses into the next generation and gets more efficient, patients like me will excel because of the knowledge that our own body is part of this solution. Seeing results, feeling results, and hearing complete remission is the ultimate goal. Maybe one day a simple transfusion of your bodys own reengineered cells will be the answer to curing the cancer for good. We can only hope, Colletti said.

Dr. Eric Ostertag, the CEO of Poseida Therapeutics, a San Diego biopharmaceutical company developing next-generation, nonviral gene engineering technologies like CAR-T, says hes not surprised by the positive emotional reaction patients have had to the immunotherapy.

CAR-T is hope for a cure. Its not just a chemo drug that you need to take every few weeks that can have horrible side effects, Ostertag told Healthline. With CAR-T, you can get long-term durable response, or a cure for some indications.

As example, Ostertag points to Byron Jenkins, a Navy pilot who was one of the first multiple myeloma patients in Poseidas clinical trial.

He is ex-military and had played football for [the] Navy. He worked out a lot. He was very fit. But after failing several therapies, he could not get out of bed. He had perhaps only weeks to a few months left to live, and he was getting weaker, Ostertag said.

But Jenkins responded well to CAR-T.

Two weeks later he walked out of the hospital, Ostertag said. Now, almost 2 years later, hes skiing again with his family, surfing, and running sprints with his son.

Ostertag says he doesnt usually get to meet the people who are treated with his companys products.

But he [Jenkins] tracked us down. He flew from the East Coast, the D.C. area, to San Diego unannounced and showed up at our front door to thank us, Ostertag said.

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How CAR-T Immunotherapy Improves Quality of Life After Cancer Treatment - Healthline

2nd person cured of HIV thanks to stem cell transplant – Medical News Today

Researchers in the United Kingdom have confirmed that a stem cell transplant has cured a second person of HIV.

In 2007, Timothy Ray Brown became the first person ever whom doctors declared to be cured of HIV. At the time, they referred to him publicly as the Berlin patient.

His journey toward a cure was not straightforward. After having received an HIV diagnosis in the 1990s, Mr. Brown received antiretroviral treatment the usual course of action for an HIV infection.

However, later on, he also received a diagnosis of acute myeloid leukemia, for which he eventually required a stem cell transplant.

As he was looking for a suitable donor match, his doctor had the idea to try an experiment. He looked for a donor with a specific genetic mutation that made them practically immune to HIV.

Receiving stem cells from this donor, it turned out, not only treated Mr. Browns leukemia but also cured the HIV infection.

Now, as a study featuring in The Lancet shows, another person has officially been cured of HIV, also thanks to a stem cell transplant.

In this second case, the person received a stem cell transplant with cells that did not express the CCR5 gene, which produces a protein that helps the virus enter cells.

The cells without the CCR5 gene were part of a bone marrow transplant, which the person was undergoing as a treatment for Hodgkin lymphoma.

Following the transplant, and at 30 months after the person ceased antiretroviral therapy, doctors confirmed that the HIV viral load remained undetectable in blood samples.

This finding means that whatever traces of the viruss genetic material might still be in the system, they are so-called fossil traces, meaning that they cannot lead to further replication of the virus.

The specialists confirmed that HIV also remained undetectable in samples of cerebrospinal fluid, semen, intestinal tissue, and lymphoid tissue.

We propose that these results represent the second ever case of a patient to be cured of HIV, says the studys lead author, Prof. Ravindra Kumar Gupta, from the University of Cambridge in the U.K.

Our findings show that the success of stem cell transplantation as a cure for HIV, first reported 9 years ago in the Berlin patient, can be replicated.

Prof. Ravindra Kumar Gupta

However, Prof. Gupta emphasizes that [i]t is important to note that this curative treatment is high risk and only used as a last resort for patients with HIV who also have life threatening hematological [blood] malignancies.

Therefore, this is not a treatment that would be offered widely to patients with HIV who are on successful antiretroviral treatment, the researcher goes on to caution.

Commenting on these findings, other researchers involved in the study express the hope that, in the future, scientists may be able to use state-of-the-art gene editing tools as part of interventions meant to treat and cure HIV.

Dr. Dimitra Peppa, who is from the University of Oxford in the U.K. and co-authored the study, notes that [g]ene editing using the CCR5 has received a lot of attention recently.

Nevertheless, she points out, there is still a long way to go before such therapies may become viable.

There are still many ethical and technical barriers e.g., gene editing, efficiency, and robust safety data to overcome before any approach using CCR5 gene editing can be considered as a scalable cure strategy for HIV, she says.

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2nd person cured of HIV thanks to stem cell transplant - Medical News Today

Haunted by a Gene – The New York Times

Year after year for two decades, Nancy Wexler led medical teams into remote villages in Venezuela, where huge extended families lived in stilt houses on Lake Maracaibo and for generations, had suffered from a terrible hereditary disease that causes brain degeneration, disability and death.

Neighbors shunned the sick, fearing they were contagious.

Doctors wouldnt treat them, Dr. Wexler said. Priests wouldnt touch them.

She began to think of the villagers as her family, and started a clinic to care for them.

They are so gracious, so kind, so loving, she said.

Over time, Dr. Wexler coaxed elite scientists to collaborate rather than compete to find the cause of the disorder, Huntingtons disease, and she raised millions of dollars for research.

Her work led to the discovery in 1993 of the gene that causes Huntingtons, to the identification of other genes that may have moderating effects and, at long last, to experimental treatments that have begun to show promise.

Now, at 74, Dr. Wexler is facing a painful and daunting task that she had long postponed. She has decided its time to acknowledge publicly that she has the disease shes spent her life studying and that killed her mother, uncles and grandfather.

There is such stigma, and such ostracization, Dr. Wexler, a professor of neuropsychology at the College of Physicians and Surgeons at Columbia University, said in a lengthy interview. I think its important to destigmatize Huntingtons and make it not as scary. Of course it is scary. Having a fatal disease is scary and I dont want to trivialize that. But if I can say, Im not stopping my life, Im going to work, were still trying to find a cure, that would help. If I can do anything to take the onus off having this thing, I want to do it.

Among her greatest concerns are the thousands of Venezuelans from the families full of the disease, whose willingness to donate blood and skin samples, and the brains of deceased relatives, made it possible to find the gene. But they live in an impoverished region, and, Dr. Wexler said, they are still outcasts. The clinic that she and her colleagues opened has been shut down by Venezuelas government.

We share DNA, Dr. Wexler said. Theyre part of my family. They are super-stigmatized. So I thought, this is part of my decision to come out, about me which I still find hard to do without breaking into tears.

If treatments now being tested do pan out, she said in an editorial in The New England Journal of Medicine, the Venezuelan patients should get them, for free.

Shes a remarkable human being whos been an incredible leader of a scientific initiative, said Dr. Francis Collins, director of the National Institutes of Health, who was among those she recruited to help find the Huntingtons gene.

Although Dr. Wexler has not talked about her diagnosis until now, it is no surprise to friends or colleagues. For at least a decade, her symptoms were noticeable. Her gait is unsteady, her speech is sometimes slurred, her head and limbs move uncontrollably at times. She loses her temper. She needs a walker to get around outside the Manhattan apartment she shares with Dr. Herbert Pardes.

But her mind is sharp and her will is strong, and she has chosen to deal with the disease or not deal with it on her own terms and in her own good time.

Weve been close friends for 37 years and it has been very hard to not have this as a topic we can share, Dr. Collins said. But shes a private person, and I think we all understood she was not ready to go there.

Part of her coming out includes appearing in a new documentary film, The Gene, produced by Ken Burns and Barak Goodman, to air on PBS this spring. Film shot later, not part of the documentary, shows her exuberantly touring a facility that makes an experimental drug being developed by Roche that she is hoping will work and become available in time to help her. The studies she led made development of the drug possible, but she is too old to qualify for the clinical trials testing it. Results are not expected until 2022.

In the film, a researcher shows her a vial of the drug. She kisses the vial and hugs the researcher. Thats my disease there, she says. Youre curing it!

The specter of the disease has been hanging over Dr. Wexler since 1968, when she was 22. One morning, a police officer accused her mother, Leonore, of being drunk as she crossed a street in Los Angeles on the way to jury duty. She had not realized she was staggering.

Leonore Wexlers father and all three of her brothers had died from Huntingtons. She was a geneticist, a field she had chosen in hopes of finding a way to save her brothers, Dr. Wexler said.

Huntingtons is caused by a dominant gene: If one parent has the disease, every child has a 50/50 chance of having it, too. The disease is rare. About 30,000 people in the United States have it, and another 200,000 are at risk. It is the disease that killed the folk singer Woody Guthrie in 1967.

At the time of Leonores diagnosis, there was no test for the gene. People who knew they were at risk could only wait to see whether they fell ill. The symptoms usually appear when patients are in their 30s or 40s after theyve already had children. Leonore was 53 at her diagnosis, past the average.

Depression, irritability and other psychological problems can occur, along with the uncontrolled movements. Patients lose the ability to speak, but remain painfully aware of their decline.

After Leonores diagnosis, her ex-husband, Milton Wexler, told their daughters, Nancy and her older sister, Alice, about the disease and that they were at risk of getting it, too. Despite the odds, he insisted that they would be spared.

But looking back at that day, Dr. Wexler said she felt that, in an instant, three generations had been wiped out: Her mother, herself and the children she had hoped to have. She and her sister decided that they would not have children. To this day, Dr. Wexler said it is a decision that she very much regrets.

Determined to find a cause and cure, or at least a treatment, Milton Wexler started the Hereditary Disease Foundation to raise money and recruit researchers. Nancy, who received a doctorate in psychology, nonetheless decided to devote her career to Huntingtons and its genetics.

Leonore Wexlers condition worsened. She tried to commit suicide, but Milton Wexler saved her by calling an ambulance. Dr. Wexler said she thought her father later regretted that decision, because her mother suffered for years afterward, in nursing homes.

As she became increasingly ill, I dressed her, carried her, helped her brush her teeth and go to the bathroom, fed her and, mostly, held her and kissed her, Dr. Wexler wrote in an essay published in 1991. Her eyes still haunt me with their sadness and fear.

Leonore Wexler died on Mothers Day in 1978, 10 years after the diagnosis.

The following year, Nancy Wexler made her first trip to Venezuela to study a large extended family, first described in 1955 by a Venezuelan doctor, Americo Negrette. The family was thought to have the worlds highest prevalence of Huntingtons disease. She knew that to find the gene, scientists would need DNA samples from as many affected people and their healthy relatives as possible.

The scientists, arriving by boat, found patients everywhere, some of them children, with the classic writhing and flailing signs of the disease, which was known locally as el mal.

Dr. Wexler told them that she and they were related, that her family had the disease, too. She showed them a tiny scar on her arm where shed had a skin sample taken, as she was asking them to do.

I fell in love with them, she said.

For 20 years, she returned with teams that ultimately collected 4,000 blood samples. They traced the path of the disease through 10 generations in a family tree that included more than 18,000 people.

Working with Nancy in Venezuela was a real testament to how an individual can take a team and get absolutely water out of a brick, said Dr. Anne B. Young, a professor and former chief of neurology at the Massachusetts General Hospital, who made 22 trips to Venezuela with Dr. Wexler. She was able to take all of us and drive us, 16 hour days out in the field where it was 96 degrees and 90 percent humidity.

Dr. Wexler was a powerful presence.

She was just totally charismatic, and when you walked into the room she would hug you and look you in the eye and listen to everything you said, Dr. Young said. She never thought about herself. She was always thinking about what she could learn from the other person. People just became totally devoted to her. Everybody felt theyd take a bullet for her.

In 1983, just four years after the first trip, the team found a marker, a stretch of DNA that was not the gene itself but nearby. It took a half dozen high-powered research groups handpicked by Dr. Wexler and her father 10 more years to find the gene itself, on chromosome 4, one of the 23 pairs of chromosomes found in most cells in the body.

The discovery was a landmark in genetics, one that scientists say would never have happened without Dr. Wexler.

Biomedical research wasnt a team sport in the 1980s, not until Nancy got involved, and then it had to be, Dr. Collins said.

Dr. Wexler and her father were relentless, he said, by insisting the research groups work together.

Each group was driven by a strong-egoed principal investigator, Dr. Collins said. You can imagine things didnt always go smoothly. But there was no way you could go to Nancy and say, I cant work with this person.

Milton Wexler had been a psychotherapist to the stars, and tapped some of his celebrity clients to help his cause.

During the annual meetings in Santa Monica, there might be a dinner at Julie Andrews house or Carol Burnetts house, Dr. Collins said. We were all starry-eyed. It was quite a perk for us nerds.

Dr. Wexler brought people with Huntingtons and their family members to the research meetings, to describe what life was like with the disease. Many of the scientists had never seen Huntingtons up close.

You couldnt listen to that as a researcher and not be impressed by the seriousness of the task, Dr. Collins said. This was not some academic exercise.

Concern for Dr. Wexler herself also drove the teams.

We knew the clock was ticking for her and for Alice, Dr. Collins said. It was a matter of watching Nancy all the time and wondering if shes escaped the curse or is it going to fall on her, too.

The gene contains the blueprint for a protein that the researchers named Huntingtin. Its role in the brain is not understood. But in people with the disease, a series of three DNA building blocks represented by the letters CAG is repeated too many times. The repeats lead to an abnormal form of Huntingtin, which poisons nerve cells in the brain.

Finding the gene made it possible to develop a test that could tell people at risk whether they would develop the disease. The discovery posed a wrenching ethical and emotional quandary that persists to this day.

Do people really want to know that a disabling and fatal disease lies in wait for them, when there is no cure, not even a treatment that can slow it down?

Researchers feared that the information would make people hopeless and depressed, and even drive some to suicide.

A breakthrough therapy, making testing worthwhile so that treatment could start early to head off the disease, has yet to arrive.

Given her drive for knowledge, many people assumed that Dr. Wexler would be among the first to take the test. But she never did. Nor has her sister.

I dont think I could have lived with that knowledge, Dr. Wexler said. I think I assumed I wouldnt get it, because I was fine.

It was easier to live with ambiguity, she said, adding, Denial is important.

As she moved through middle age, she felt all eyes were on her and resented it.

Everybody watched me like a hawk, she said.

Gradually, the symptoms appeared. She became aware of them only when she saw herself on video or even in the mirror, and would think, Oh gee, why am I moving? There was no single moment of realization; there were many. It is not uncommon for people to recognize they have the disease only when they see photos or videos of themselves, Dr. Young said.

Every time I saw myself on video, I looked a little bit worse, Dr. Wexler said.

Others noticed the movements, the spilled drinks, the wobbly handwriting.

I love her so much that I had trouble convincing myself that she had it, said Dr. Young, who is an expert on the disease. I would try to make it go away in my mind. And I think a lot of people did.

But some colleagues bluntly asked Dr. Wexler if she had the disease. A few went so far as to tell her she did. She would say she did not, only to be told that denial was a symptom. If she happened to cross her legs, some accused her of trying to hide tremors. She found it infuriating.

Dr. Pardes warned the meddlers to back off. People learned to avoid the subject.

It was always the big elephant in the room, Dr. Young said. It made everything uncomfortable for all her best friends, who just withdraw a little bit because they dont want to hurt her.

Her sister encouraged her to open up.

I think that one thing her coming out about it will show is that getting a diagnosis of Huntingtons disease is not a death sentence, Alice Wexler said. Its something people can live with for a long time, if they have the right medical care and social services. She has been living her life in a productive way, and still will.

And so she is, reviewing grant applications, raising money for research and attending scientific conferences. Dr. Wexler holds out hope for the work on new drugs. There is still much to be learned, she says, and she still has a great deal of work to do.

Enjoy life while you can, she advises. Find what gives you some pleasure and go for it. Dont get kidnapped by this.

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Haunted by a Gene - The New York Times

Penn is fighting pancreatic cancer – Penn: Office of University Communications

Swept up in a pancreatic cancer diagnosis is inevitably a sense of fear and sadness.

But at Penn, researchers are bringing new hope to this disease. And with patients like Nick Pifani, its clear that theyre moving in the right direction.

Pifani, from Delran, New Jersey, first noticed some lingering stomach upset in February 2017. He called his family doctor, concernedespecially given that he was an otherwise healthy marathon runner who was only 42. He was sent to a gastrointestinal specialist. A few weeks later, some crippling stomach pain sent him back to the emergency room and he received an MRI that showed a mass on his pancreasStage Three, inoperable, he was told.

He was treated with chemotherapy, along with radiation and, eventually, and after receiving advice from doctors at Penn, his tumor was removed. Thereafter, he realized he had a PALB2 mutationa cousin of the BRCA gene mutation. At that moment, his long-term needs changed and he found himself seeking specialized care at Penn, where he met Kim Reiss Binder, assistant professor of medicine at the Hospital of the University of Pennsylvania (HUP).

Im a planner; I want to understand what [my] potential options are, Pifani says. [Reiss Binder] asked why I was there to see her and I explained and quickly I could tell she wasoutside of her being remarkably intelligenta great listener and a compassionate doctor.

I have a feeling she worries about me more than I do, he laughs.

Pifani has now been in remission for two years and four months; he sees Reiss-Binder every three months for checkups. His survival story is inspiring and a sign of momentum, even if a world without pancreatic cancer is still frustratingly out of reach.

Pancreatic cancer is the third-leading cause of cancer-related death in the United States, outmatched only by lung cancer (No. 1) and colorectal cancer (No. 2). A person diagnosed with pancreatic cancer is still unlikely to survive past five yearsonly 9%of survivors do, giving it the highest mortality rate among every major cancer.

In short, pancreatic cancer seldom paves the way for optimistic narratives. Some of the hope that has surfaced, though, is thanks to some talent, dedication to the cause, and hard work at Penn.

A key point of progress in the battle against the disease was made in 2002, when former Assistant Professor of Medicine David Tuveson established a standard model for examining human development of this disease in mice. This model has allowed for a reliable way to study the disease and has influenced progress made here at Penn and elsewhere since.

Theres been a burst of activity in translational research, from bench to bedside, explains Ben Stanger, the Hanna Wise Professor in cancer research and director of the Penn Pancreatic Cancer Research Center (PCRC) at the Abramson Cancer Center.

And theres a lot of momentum with community building, a dramatic increase in patient volumes, and a dramatic increase in what we know about the cancer, he says of the status of pancreatic cancer today.

Reiss Binder, meanwhile, explains that one mark of progress at Penn and beyond has been learning about people like Pifani, who have the PALB2 gene, and why they respond differently to treatments than those without it. Platinum-based chemotherapies, for example, are especially effective for people with the PALB2 gene who are battling pancreatic cancer. An ongoing trial at Penn has tested and found some success with using PARP inhibitorstaken orally as an enzyme that fixes single-stranded breaks of DNAas a maintenance therapy in that same PALB2 demographic after theyve had chemotherapy. These are less toxic than chemotherapy for patients with the same mutations.

Its all been slow progress toward better treatments, but there has been progress.

This is the tip of the iceberg for a disease that we historically have treated with perpetual chemotherapy,Reiss Binder says. We owe it to patients to find better options to suppress the cancer but not ruin their quality of life.

The consensus on why pancreatic cancer is so deadly? It just cant be spotted fast enough.

Pancreatic cancer often presents well after it has developed and metastasized, and does so in a way that is not easy to recognize as cancer. Common symptoms include, for example, stomach upset and back pain. And by the time a harder-to-ignore symptom of the cancer surfaces, a sort of yellowing of the skin (a result of a bile duct blockage), its likely too late to stop the cancer in its tracks.

One approach to improved detection being tested at Penn, by Research Assistant Professor of Medicine Erica Carpenter, is a liquid biopsydrawn from a standard blood test. Current means to test for pancreatic cancerimaging through an endoscopic tubeare invasive and expensive, meaning a common liquid test could transform how many cases are detected early.

Carpenter explains that circulating tumor cells (CTCs) can shed from a tumor thats adjacent to the wall of a blood vessel; whats shed then shows up in a blood test. The cells, if detected, can explain more about the nature of the tumor, giving doctors an opportunity to examine characteristics of cancerous cells and decide how to effectively treat a tumor if it cant be surgically removed. It also allows interpretations of disease burden and the effectiveness of medicationsthrough genome sequencingthat imaging does not.

Ultimately, this gives doctors the potential to track the growth of a tumor before its fully developed, all through one tube of blooddetected through an innovative use of technology.

David Issadore, associate professor of bioengineering and electrical and systems engineering in the School of Engineering and Applied Science, has worked since 2017 to develop a chip that detects cancer in the blood, using machine learning to sort through literally hundreds of billions of vesicles and cells, looking for these CTCs. The chip retrieves data and the machine learning developed interprets that data, attempting to make a diagnosis that not only finds pancreatic cancer but also provides information about its progressionand, importantly, whether a patient might benefit from surgery.

Right now, that test has a 24-hour turnaround, he says, but could eventually advance to having a one-hour turnaround. That would be a remarkable mark of progress for discovering the disease earlier when the chip enters a commercial stage.

Pancreatic cancer is a tough disease, and catching it early is hard, Issadore acknowledges. So, we think optimistically but also very cautiously, knowing what a challenging disease its been to make progress on, which is what drew us to the disease in the first place.

Im not an oncologist, he adds, but Im a bioengineer, and people like us who have a different perspective, the hope is we can do something truly [novel] to shift the [state of the disease].

He would eventually like to test the chip in people with other types of cancers, like lung, bladder, and liver.

For now, Penn still uses imaging as the standard of care but Carpenter is confident that blood testing is where were heading, starting with at-risk patients with diabetes and other risk factors.

The most important thing with this would be that when you put a patient on therapy, its good to know as early as possible how likely it is theyre going to respond, she explains. Tumor markers are increasingly valuable because you can avoid toxicity of the therapy, the expense of it, and most importantly you then have the opportunity to put the patient on something that might have more of an effect for them.

The challenge, she adds, is in pancreatic cancer we dont have that many effective therapies.

Another challenge, she adds, is to find the presence of exosomes, small pieces of tumor cells released into the blood stream, which she says are found in abundance among people with pancreatic cancer and could particularly be targeted among people living with diabetes or an intraductal papillary mucinous neoplasm (IPMN). So, at-risk candidates who may not present with the disease currently but are at risk. Several clinical studies and trials are currently taking place at Penn evaluating this.

A related area of interest is determining if people with diabetes, in particular, are developing cancer as part of the diabetes, or developing diabetes from the cancer. Risk factorsdiabetes, genetic markers, etc.continue to be an important area of study with pancreatic cancer.

Immunotherapy is rapidly changing the way patients are treated. And interest in immunotherapy for pancreatic cancer is growing exponentially.

But, its complicated.

We are still learning about the immune system in pancreatic cancer, explains Gregory Beatty, assistant professor of medicine and director of the Pancreatic Cancer Clinical Trials Program within the PCRC.

On one hand, we know that inflammation in the pancreas is a driver of pancreatic cancer. But we also know that T cells in the immune system can attack pancreatic cancer, he says.

The challenge that has surfaced is that T cells in patients living with pancreatic cancer are often weakened or slowed down; they dont divide or proliferate very well; and they have a hard time finding the cancer. That makes harnessing them for therapy a challenge. One idea, though, is to engineer ones own T cells (as inCAR T therapy), while theyre still healthy, to detect and kill pancreatic cancer cells.

Penn recently completed a trial in ovarian cancer, mesothelioma, and pancreatic cancer, using CAR T cells engineered to recognize a protein called mesothelin, which is expressed by pancreatic cancer. The team found that the T cells, when injected into the blood of patients, were safe but had limited activity.

These CAR T cells can kill pancreatic cancer in the lab really well. But why they dont do so in patients still remains a mystery, Beatty says.

It does prove that pancreatic cancer evades the immune system extraordinarily well.

Penn investigators have also done work on CD40, a protein expressed in a wide range of immune cells, explains Robert H. Vonderheide, director of the Abramson Cancer Center, who has been working with Mark O'Hara, an assistant professor of Hematology-Oncology, on CD40 therapeutics. Patients are responding to treatment with CD40a protein that activates T cells to work more steadfastly and seek out cancer cells.

It seems to make chemo work better, Beatty explains.

This is a very promising treatment for convincing the immune system to attack pancreatic cancer, Beatty adds, And in the lab, we are finding ways to make it work even better.

The larger idea is to build on a backbone of chemo and CD40 in the future to help coax T cells to work better. Overall, a major thrust of treatment for patients at the PCRC is focused on unraveling ways to use immunotherapy while developing the next-generation of strategies for patients with BRCA 1 and 2 genes who are receiving PARP inhibitors.

The stress of a pancreatic cancer diagnosis can be dizzying. It is, says Pancreatic Nurse Navigator Trish Gambino, a cause to act fast.

We really believe pancreas cancer is a medical emergency much like a heart attack, she says. As a nurse navigator, I try to get newly diagnosed patients with pancreatic cancer expeditiously to the correct provider for staging and treatment.

Because of that, she says, patients are often still digesting their diagnosis while also juggling appointments, choosing a doctor, making decisions about care, settling personal matters, and communicating with insurance companies. Gambino, one of eight nurse navigators hired to put organization and compassion on the frontlines, takes multiple incoming callsas many as fiveper day from people who have been diagnosed and sound shell-shocked.

I get so many of these calls per week saying, Trish, I just went to the doctor and they told me I have a pancreatic mass on my CAT scan. And I dont know what to do, she says. A lot of times patients dont know what they need.

Her job is one of compassion but also pragmatism. She listens and places their concerns in context and individualizes her approach to moving patients in the right direction, laying out all the options and giving them a sense of order and control over their narrative.

It really does take a village to try to get people through this, Gambino explains, noting how overwhelming the cancer experience can be. When you have pancreas cancer, its not just the medical oncologist, the radiation oncologist, the surgeon, the dietician, the social worker, the nurse navigator, the infusion nurses, the nurse practitionerstheyre all there and the response is often Who is everybody? They need someone who can lead the team for them.

She says that Penn is especially well-regarded for its interdisciplinary teamseven factoring in diet and financial wellnessand their ability to act swiftly. Penn, for instance, performs more than 150 pancreatic cancer surgeries per year and is practiced at itnot typical of every hospital and a draw for newly diagnosed patients who are eligible for resection.

Looking ahead, Stanger is optimistic about advances in screening and immunotherapy treatmentparticularly research funded by the Parker Institute for Cancer Immunotherapy, started by Sean Parker, a cofounder of Facebook. Penn is one of 10 sites of major investment for research and was the impetus for the investment in pancreatic cancer.

Hes also encouraged that the research community surrounding pancreatic cancer is collaborative, he says, with many doctors recognizing the enormous challenge of the disease and working together well.

Celebrity diagnoses, like that of Alex Trebek, als0lend some hope in the messaging of how the disease is presented to the world today.

I talk to people almost every day, and when we talk about pancreatic cancer they say, Oh, thats a really bad one, he says. One thing I respect about Alex is he came out and was very forthcoming and he spoke with a great deal of confidence and hope in the medical community and gave a positive message that said, Im going to do my best to beat this.

Pifani, meanwhile, more than two years out from his surgery, is feeling optimistic. Hes mostly resumed a normal lifewith occasional side effects that linger, of course, and scans every six months. He runs marathons and spends time with his wife and kids. And, a member of the Survivor Council at the Pancreatic Cancer Action Network and sponsorship chair for the Philadelphia affiliate, he shows up to community events built around raising awareness of the disease and advocating research and caregiver support.

At Penn, he says, he feels like hes in the right place with his carethat hes in the best hands if something does happen, and recognizing the diseases ongoing presence in his life.

I got a long way to go, he says, but were off to a good start.

Homepage photo: Gregory Beatty, assistant professor of medicine and director of the Pancreatic Cancer Clinical Trials Program within the Penn Pancreatic Cancer Research Center, examines a blood sample.

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Penn is fighting pancreatic cancer - Penn: Office of University Communications

Podcast: A family on the frontier of hyper-personalized medicine – MIT Technology Review

Deep Tech is a new subscriber-only podcast that brings alive the people and ideas in our print magazine. Episodes will be released every two weeks. Were making the first four installments, built around our 10 Breakthrough Technologies issue, available for free.

Three-year-old Ipek Kuzu has an extremely rare genetic mutation that disrupts a protein needed for DNA repair, causing the loss of brain cells. Now shes become only the second person in the world to receive a customized antisense oligonucleotide drug designed to compensate for the DNA mistake by allowing her cells to splice together a functional version of the protein. The drug took Boston-based pediatrician and geneticist Tim Yu only months to create, heralding a new era of individualized genomic medicine. But it cost $2 million to manufacture and testleading to questions about how soon hyper-personalized treatments for rare genetic disorders can be made accessible and affordable. Journalist Erika Check Hayden got to know the Kuzu family, and in this episode she chronicles Ipeks journey, with help from Ipeks father Mehmet and Technology Review biomedicine editor Antonio Regalado.

Show notes and links:

If DNA is like software, can we just fix the code?, from the March/April 2020 print issue, p. 46

Hyper-personalized medicine, from the March/April 2020 print issue, p. 18

Sign up for The Download your daily dose of what's up in emerging technology

Two sick children and a $1.5 million bill: One family's race for a gene therapy cure, from the November/December 2018 print issue, October 23, 2018

Episode Transcript

Audio ID: This is MIT Technology Review.

Mehmet Kuzu: Around five to six months, they said she has something called ataxia telangectasia. And they said this doesnt have any cure. The initial days were very tough. We were crying all the time. So then after a while, we started investigating what can be done.

Wade Roush: Mehmet Kuzus three-year-old daughter, Ipek, has a rare genetic mutation that could end her life by age 25. But now shes getting a so-called antisense drug that her doctors engineered specifically for her. Which makes Ipek one of the first patients being swept up in a new wave of hyperpersonalized medicine. Journalist Erika Check Hayden wrote about the Kuzu family in the latest issue of Technology Review. And today, she helps us understand where this breakthrough came from, and how soon it might be scaled up. Im Wade Roush, and this is Deep Tech.

[Theme music]

Were right at the beginning of a revolution in individualized genomic medicine. And if you want to know what that revolution sounds like, this is a good place to start.

[Sound of Illumina sequencing machines]

Thats one of the hundreds of high-speed gene sequencing machines at the Broad Institute of MIT and Harvard. Here at the Broads genomics platform in Cambridge there are so many of these machines that the institute can read the equivalent of 30 whole human genomes every 10 minutes.

There arent a lot of research centers with that kind of power. But in many places around the world its now possible to scan a babys full genome for just a few hundred dollars, and locate DNA coding errors that can cause rare conditions like ataxia telangectasia.

Thats how doctors diagnosed Ipek Kuzu when she was just six months old. The mistake in her DNA means her cells cant make a protein called ATM thats essential for DNA repair. Over the long run that causes the loss of brain cells, which means Ipek has some trouble walking and doesnt talk as much as a typical three-year-old.

Today Ipek is receiving an antisense drug made just for her. Its designed to compensate for the DNA mistake and restore production of ATM. Which makes her only the second person in the world to get this kind of treatment. The first was another little girl named Mila Makovec. She has different genetic disorder called Batten disease that causes blindness, seizures, and other neurodegenerative problems. And Mila got her own customized antisense drug starting in 2018.

But to understand how her doctors came up with these two medicines, and why this whole field of hyperpersonalized medicine is so hot that the editors of Technology Review decided to put it on this years list of 10 breakthrough technologies, we first have to jump back a few years, to 2016.

[CNBC Squawk Box news clip]

CNBC male anchor: Ionis Pharmaceuticals, in pre-market trading, is higher. The FDA has approved a drug called Spinraza. Spinraza.

CNBC female anchor: Its not Spine-raza?

CNBC male anchor: Maybe it is. Because its for spinal muscular atrophy. Its the first drug approved to treat the rare and fatal disease.

Wade Roush: Spinal muscular atrophy affects about 1 in 10,000 babies. So its not nearly as rare as Batten Disease or ataxia telangectasia. But Spinraza is literally the key to all of the more recent work to make customized antisense drugs for Mila and Ipek. So lets take a minute to go over how it works.

What made Spinraza a big deal is that it was one of the first successful medicines made using an antisense oligonucleotide. In other words, a customized strand of RNA.

Antonio Regalado: If you can imagine, inside a cell, there's the DNA.

Wade Roush: This is Antonio Regalado, the editor for biomedicine at Technology Review.

Antonio Regalado: And it kind of sends out these messages into the nucleus made of RNA and those are used as the templates to make proteins. And so antisense is a drug that acts at the level of RNA. They're going to stick to that RNA message and they could block it.

Wade Roush: Keep it from being translated.

Antonio Regalado: Keep it from being translated, or modify the translation in some fashion.

Wade Roush: In the cells of healthy people, theres a protein called SMN that helps motor neurons survive and grow. A gene called SMN1 carries the instructions for making that protein, and people with spinal muscular atrophy have a mutation that disables that gene. But it just so happens that human DNA also contains a second copy of the gene, called SMN2. This second copy is typically inactive, thanks to a small error that keeps the RNA message from being spliced together into a proper template. The Spinraza molecule contains a short segment of antisense RNA that prevents the splicing error. And that allows the body to start making the motor neuron protein.

Ionis Pharmaceuticals is the company that makes Spinraza, and they put a lot of work into figuring out how to get their molecule into cells in the brain and the nervous system, where it can do its work.

Antonio Regalado: And they finally mastered it and came up with pretty much kind of a miracle drug for one of these rare brain diseases that affects kids, spinal muscular atrophy. And so from that example, people then said, well, why can't we use antisense for other diseases that are similar?

And what we learned was that there was a doctor in Boston named Timothy Yu, who was an expert in sequencing genomes of sick children. And there was one girl named Mila Makovec. And her parents had come to him. He'd sequenced the genome. And then he just realized, I don't have to stop here. Once I've identified this defect, I don't have to stop. I could potentially make a drug. And so that's exactly what he did.

Wade Roush: It turned out that Milas disease was caused by a splicing error very similar to the one that causes spinal muscular atrophy, except that in Milas case it disrupts a different protein called CLN7. Tim Yus idea was to take the backbone of the Spinraza molecule and attach a customized strand of antisense RNA. With this new business end, so to speak, the drug would enable Milas cells to start making functional copies of the CLN7 protein.

Antonio Regalado: That was probably at that point just the clearest, starkest, most stunning example of this hyper personalized medicine. Because in this case, it was really for one person. So we were very interested in this phenomenon, because it's a reflection of what technology can do. And then in the middle of last year, a pretty prominent journalist, Erika Check Hayden, came to us and she was also interested and wanted to do some work to find the cases, find the families and write more stories about it. And as it developed, we decided, well, let's put this on our list of breakthrough technologies, because it really is. And so Erika ended up writing the piece and she did a lot of work to find the patients. One of the great things she did was to find this Kuzu family, which happens to be right here in Cambridge.

Wade Roush: Erika, could you introduce yourself and tell us a little bit about you?

Erika Check Hayden: Sure. My name is Erika Check Hayden. I'm a journalist based in San Francisco. And I also run the science communication program at the University of California, Santa Cruz.

Wade Roush: When you set out to start reporting this piece, did you feel like it was important to go beyond the first sort of headline-making case of Mila Makovec and look for additional patients who were going through this process to see how broadly applicable the whole idea is?

Erika Check Hayden: I do think that while people have been very impressed by Mila's case and by the drug that Tim Yu made for her, which is called milasen, I think there's also been this question of are we gonna be able to do this for other patients? And if so, you know, who is going to be treatable via this method? And so if I'm going out and finding other families that are hopefully replicating that success, I think is a really important statement about how impactful this approach might eventually be.

Wade Roush: So this is where the Kuzu family comes in. So could you tell us a little bit about them and how you got in touch with them?

Erika Check Hayden: So the Kuzu family, they originally came from Turkey and the father in the family, Mehmet Kuzu, is now a software engineer at Google. And they were living in Silicon Valley when their daughter Ipek was born. And soon after she was born, she was diagnosed with this disease called ataxia telangectasia, which is also called A-T disease. And when that happened, they set about trying to understand if there was anything they could do to treat the disease or slow the disease. And that's what led Mehmet down this path that eventually led him to work with Tim Yu.

Mehmet Kuzu: I sent the genetic report of our daughter. Then he said, oh, there's a potential here, but there are two main problems. He said this might cost around like two million, and the insurance will not cover it. The second problem, it might cause damage because, we have a theoretical idea, but biology is complicated. So at the end of the day, it might be worse than what is expected.

Wade Roush: Right. So for the Kuzu family, while it was obviously bad news that your kid is getting diagnosed with A-T disease, there is this amazing foundation or non-profit led by Brag Margus, the A-T Children's Project, that has all this data and also apparently has some fundraising clout. And they wind up helping to finance a lot of this research and even finance Ipeks treatment.

Erika Check Hayden: Right. And I think that's part of why this particular project was able to move so fast, because Brad Margus and the A-T Children's Project had done a lot of work over the years to fundraise and educate their community about the potential for treating this disease, so that when they found something that he actually thought could work, they were able to raise $1.4 million in a relatively short amount of time to fund the development of this unique drug.

Mehmet Kuzu: I think he understood to the promise of it. And then he agreed to financially support us. But the problem is this money in the pool is coming from many families. So we should have a fair selection. Then they found three kids that young in age, like three, two, two, three, four, with the right mutation type, and they got skin samples from all of them, and tested it. They were able to do it quickly.

Wade Roush: Mehmet can recount all these events pretty calmly. But I think its worth underscoring what a roller coaster the familys been on. The backing of the AT Childrens Project opened a window for Tim Yu to design and manufacture an antisense drug. But the required safety testing is so expensive that only there was only enough money to do that for one patient. There was a two in three chance that Ipek would not be that patient. And even if she did get selected, there was no way to know whether the treatment would be effective. Mila Makovec had been having fewer seizures since she started getting her antisense treatment, but doctors still werent 100 percent sure that it was because of the medicine. On top of all that, there was still the risk of unintended side effects.

Mehmet Kuzu: and then at the end of the day, Ipeks cells responded the best among these three candidates. Now, once we know we are selected, now we concentrate on second issue: do we really want to take this risk of, like, making things worse? And then I thought, like, most probably something good will happen. Of course there is a probability of, a possibility [of failure]. But imagine if that happens: science will learn from this. And her kind of sacrifice, and that would help, too, many other people.

Erika Check Hayden: It's been just incredible over the past few years to meet these families, understand what they're doing, how they're doing it. I've just been really struck by everything they've been able to accomplish. And also the mindset that they bring to this where, you know, you'll talk to, or I will talk to, parents who are doing this for their kids and they've had scientists tell them, 'You've got to be prepared for the possibility that this isn't going to help your kid. You know, you might be doing all of this work on behalf of some other future child. This might not come in time to help your own child.' And they persist and are really driven.

Wade Roush: Ok. So in the same way that Tim Yu helped to create this unique drug called milasen for Mila Makovec, he's created a drug called atipeksen for Ipek. If that drug if that drug works, how will it help Ipek?

Erika Check Hayden: If this drug works, basically what it's going to do is correct the way that Ipek's cells interpret her genetic information so that she will make a functioning copy of the ATM protein. Now, how we will know if this is working is a bit of a tricky question. So, Tim Yu and other doctors are going to try a variety of methods to see if they can tell whether the drug is actually helping her. So, for instance, they will look at things like can they see evidence in Ipek's body that the drug is actually making corrected versions of the protein? They will look for evidence that she isn't declining in the ways that we might expect her to if she wasn't getting treatment to help control her disease. But it might be tricky to tell whether it actually works or not.

Mehmet Kuzu: She had three injections until this point because they are starting with very low dose and escalating itAnd fortunately, we haven't seen any adverse effects in the first three. But like, of course, knowing if this is really working or not, they told us that it will take time. Maybe we need a year to understand if it's really working. But at least we have seen that no bad thing happened. At hospital she's going on the full anesthesia. They're putting on a mask. And after the injection they are taking bloods every four hours, three or four times. These are very stressful for her. She's fighting not to have this mask. She's crying a lot. Uh, but once discharge happens, once we come home, she forgets about everything. She just plays with her toys.

Wade Roush: Right. And this is one of the things you mentioned in your piece. Not only will it be tricky to see whether it's working or not, but we're talking about by definition an n of one study where there's only one patient. So you don't get the kinds of large numbers that help researchers feel more confident that a drug is safe and effective.

Erika Check Hayden: I think what we still don't know very well yet is which diseases are going to be helped most by this approach, or even if any of these individual customized treatments can cure a patient. So if you talk to Mila's mom, Julia Vitarello, she is very convinced that that drug has helped Mila. But I think accumulating that data to the level where we really know that this is a worthwhile approach, you know, that's probably going to take a while.

And to take a step back, I think that's part of the reason why these drugs are only being used right now in patients that have really severe progressive diseases, because you are taking a certain risk by giving a treatment to a patient when you haven't done the kinds of safety testing that we might be used to for a drug that would normally go through an FDA approval process. In fact, there are some people who object to even using the word treatment because we don't necessarily know that these drugs are going to cure the patients.

So in the meantime, I think everybody would like to see far more patients at least be able to try this. And so there's this question as to whether it's only going to be patients who have the resources to raise that money or access that money that are going to benefit. And I don't think anybody wants that to be the case.

Wade Roush: Are there any signs that the drug industry is looking at how to scale up some of these treatments? And, you know, maybe create a pipeline for hyper personalized drugs?

Erika Check Hayden: So we're seeing things like Ionis, their co-founder Stan Crooke has started a foundation called the n-Lorem Foundation that's going to try to develop these treatments for patients. The reason is that developing a drug for one patient that costs millions of dollars and doesn't really have a very large market is not something that's necessarily going to be attractive to a company. But I think people think there is a direction that could evolve where, you know, if the drug industry is better able to manufacture these drug templates or backbones and more easily switch out the part of the drug that's the business end that's doing the targeting of different genetic diseases to where that becomes much more large scale, much more customizable, much cheaper. You know, then you might see a model where this is much more economical, affordable, reimbursed by insurance companies, because right now this is not and obviously that's a major cost barrier.

Wade Roush: Do you think this is a time for patients with rare genetic disorders and families of those patients to feel more hopeful? Or is it just too early realistically for this to affect lots of people who are already suffering from these conditions?

Antonio Regalado: Right. It goes back to the question, should this be a breakthrough technology? Because right now, it's not helping that many people. We're talking about helping one person. Or we're talking about helping two or three very few people. Very few. And that's a strike against the idea, frankly. Like, why? Why should we invest resources into this when it helps so few people? Why should we call it a breakthrough technology? Well, the reason to is, it's sweet. Technically, it's sweet. And it paints a path towards a future where it like you can do a lot more with genetic drugs.

Wade Roush: So you can imagine a future not 100 years away, but maybe 10 years away, where this can be scaled up and broadened out to more patients.

Antonio Regalado: Yeah, absolutely. I mean, will the drugs work? How well will they work? It's kind of an open question. But yeah, we've already gone from one case to five cases next year no doubt it it'll be 10 and then a hundred and then thousands. Most likely. I want to raise something else, which this whole scenario is not fair. Because there's a lot of people with rare diseases and a lot of kids dying of rare disease in every neighborhood and every corner and every precinct of the country, of the world. So who has the opportunity to have this chance?

Wade Roush: Well, who does so far?

Antonio Regalado: Well, it is a very small subset of parents who for whatever reason have the ability to wrap their head around the science, to find where the opportunity is, and to raise quite a lot of money. And this is not bake sale money. This is two million dollars. Three million dollars. You have to really have a way to do that, and it favors people with a big network. That's why we're seeing people, you know, entrepreneurs from Silicon Valley or other people who just for whatever reason, manage to pull it off.

Wade Roush: If this kind of inequity persisted, it would definitely become a huge point of criticism around this whole area of therapy. But maybe you could look at these parents as the pioneers.

Antonio Regalado: Right. Exactly. A lot of the parents will say, well, in addition to trying to help my child, I also want to invest and try and create the process by which everybody else can be helped because they also have a lot of empathy for the next person. The idea is to help everybody. The pathway to doing that is not clear yet.

Wade Roush: All right. Well, whether this is a breakthrough or not, it raises so many interesting and thorny questions that it's perfect fodder for Technology Review.

Antonio: It's definitely a breakthrough, man. It's definitely a breakthrough.

Wade Roush: Okay. Thanks Antonio.

[Theme music]

Thats it for this edition of Deep Tech. This is a podcast were making exclusively for MIT Technology Review subscribers,to help bring alive some of the people and ideas youll find in the pages of our website and our print magazine. But the first four episodes cover our annual 10 breakthrough technologies issue, and were making those episodes free for everyone.

Deep Tech is written and produced by me and edited by Michael Reilly, with editorial help this week from Jennifer Strong. Our theme is by Titlecard Music and Sound in Boston. Special thanks this week to David Cameron, Howard Gelman, Erika Check Hayden, Mehmet Kuzu, Antonio Regalado, and Jane Wilkinson. Im Wade Roush. Thanks for listening, and we hope to see you back here for our next episode in two weeks.

See original here:
Podcast: A family on the frontier of hyper-personalized medicine - MIT Technology Review

Former UK-based chef is second person in the world to be ‘cured’ of HIV – Mirror Online

A former chef living in the UK has become the second person in the world to be 'cured' of HIV, according to scientists.

Adam Castillejo has remained free of HIV for two-and-a-half years since he was given ground-breaking therapy at Hammersmith Hospital in west London.

The 40-year-old, who was born in Venezuela but lives in England, received a transplant of bone marrow stem cells that rid him of the AIDS-causing virus.

The donor's DNA carries a gene mutation that makes blood highly resistant to the virus.

His doctor Professor Ravindra Kumar Gupta, of the University of Cambridge, said: "We propose these results represent the second ever case of a patient to be cured of HIV."

American Timothy Ray Brown, now 54, became the first person to be cured of HIV/AIDS in 2011.

He was dubbed "The Berlin Patient" because he lived in the city at the time - and was treated there.

Prof Gupta said: "Our findings show the success of stem cell transplantation as a cure for HIV, first reported nine years ago in the Berlin patient, can be replicated."

Mr Castillejo has received bone marrow stem cells for the past three years from a donor who carries a rare gene called CCR5 that stops HIV in its tracks.

He has also spent 18 months without taking anti-retroviral drugs - the medication that controls the virus and stops it progressing.

Mr Castillejo told the New York Times he was in a "unique and very humbling position."

He said: "I want to be an ambassador of hope."

As a young man, he made his way first to Copenhagen and then to London in 2002 he was found to be HIV positive in 2003.

Reporting his case in The Lancet HIV, Prof Gupta says long-term follow-up "suggests no detectable active HIV virus remains in the patient."

He added: "Although the treatment is high-risk and only suitable for certain patients, the results provide evidence this patient is the second to be cured of the virus - replicating the finding that HIV cure is possible through stem cell transplantation."

Prof Gupta pointed out Mr Castillejo and Mr Ray Brown were given stem cells to treat cancer, not HIV.

Stem cell and bone marrow transplants are life-threatening operations. Dangers lie in the patient suffering a fatal reaction if substitute immune cells don't take.

Medication that lowers the virus to an undetectable level is a safer option for those living with HIV.

Prof Gupta said: "It is important to note this curative treatment is high-risk, and only used as a last resort for patients with HIV who also have life-threatening haematological malignancies.

"Therefore, this is not a treatment that would be offered widely to patients with HIV who are on successful anti-retroviral treatment."

But the successes shed light on how a more widely applicable cure might be developed in the future, say the team.

Mr Castillejo has a healthy number of immune cells, suggesting he has recovered well.

What's more, 99 percent are derived from the donor's stem cells, indicating the transplant had been successful. This suggests a "99 percent probability of cure," said the researchers.

But Mr Castillejo will need continued, but much less frequent, monitoring for re-emergence of the virus.

Co-author Dr Dimitra Peppa, of the University of Oxford, said: "Gene editing using the CCR5 has received a lot of attention recently.

"The London and Berlin patient are examples of using the CCR5 gene in curative therapies outside of gene editing.

"There are still many ethical and technical barriers - for example gene editing, efficiency and robust safety data - to overcome before any approach using CCR5 gene editing can be considered as a scalable cure strategy for HIV."

Some 37 million people worldwide are currently infected with HIV and the AIDS pandemic has killed around 35 million people worldwide since it began in the 1980s.

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Former UK-based chef is second person in the world to be 'cured' of HIV - Mirror Online

Berks County mother fights insurance companies to cover $2 million gene therapy drug for son – KESQ

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WERNERSVILLE, PA (WPMT) A Berks County mother is battling with insurance companies to get her son the treatment he needs. Doctors have prescribed the toddler the most expensive drug in the world. Yet, his insurance companies deny coverage.

What is my childs life worth to you, asked Jacqueline Brewer, of Berks County.

Brewer has been in a fight with her almost two-year-old son Johns insurance companies for nine months.

Were not giving up, said Brewer.

John was a happy, healthy baby for the first six months of his life.

He was drinking from a bottle, he was nursing, he was great until he picked up a viral infection, said Brewer. it was just a simple cold.

A cold that took a turn for the worse very quickly, appearing to trigger something even worse in John.

Being in the ICU and being intubated and the doctors coming in and saying were going to do more tests and more tests and more tests and theres still nothing coming up, said Brewer. And then they said theyd like to do a genetic panel.

The genetic panel revealed John has spinal muscular atrophy, also known as SMA. Its a muscle wasting disease caused by a mutated chromosome gene.

It goes on and on and on until he basically cant move, said Brewer. He wouldnt be able to move his tongue. His diaphragm would no longer work. And its terrifying.

Johns been receiving a drug called Spinraza every four months, it helps build the proteins his body needs.

Its a little much, it takes a toll on him, said Brewer. Hes getting a stronger. Now, hes able to hold his head up a little bit.

Spinraza has a price tag of more than $100,000 per injection and is covered by Johns insurance. But, since May of 2019, theres something new on the market.

Now theres Zolgensma. Thats the one we need and that would stop the regression, said Brewer.

Zolgensma is the most expensive drug in the world, with a $2.1 million price tag, but John would only need to receive it once. The one-time treatment is actually less expensive than receiving Spinraza for five years.

It would stop where hes at, said Brewer. He would never get any worse and thats what we need.

Yet, insurance companies Aetna and Ameri-Health have continuously denied coverage of the drug.

Every doctor he comes across is saying its medically necessary for this child to have it but theyre [insurance companies] saying no, said Brewer.

Brewer has continued to receive denials letters from Johns insurance companies all saying the same thing: The request for Zolgensma was denied completely because we are not able to establish medical necessity.

Theyre saying its not medically necessary because hes already being supported, said Brewer. Hes already on a ventilator and the Spinraza injections are enough.

But, Brewer says other children with advanced stages of SMA with other insurance providers have been approved for Zolgensma.

Time is also running out for John to receive Zolgensma. The FDA only approved it for children under two-years-old. John turns to March 24th.

Its terrifying because what if they say no and dont budge and hes gonna turn two and theyre not going to budge, said Brewer. But, Im still going to call everyday, his doctors are still calling everyday, they will do everything they can. Were not going to give up. Even if he turns 2, Im not going to give up.

Brewer says she will continue to fight Johns insurance companies every single day, and if he doesnt receive the drug before he turns two, shell look for clinical trials to somehow get John this drug.

I need to know what this innocent childs life is worth, said Brewer

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Berks County mother fights insurance companies to cover $2 million gene therapy drug for son - KESQ

Retired attorney with rare muscular disease FHSD connects with others and accelerates search for cure – TribLIVE

Mark Christman resented being thought of as a wimp.

As a kid growing up in Indiana Township, hed always felt more like a tough guy, with the inner tenacity, drive and work ethic of a competitive athlete. Christman loved playing sports, but getting picked last on nearly every team was frustrating.

Around age 14, tasks like running laps and picking up a shovel to clean up after the family horse became unnervingly difficult. Hed lift weights for months and gain little to no muscle. And despite being relatively skinny, he had a small pot belly protruding from one side of his stomach.

In 10th grade, Christman joined the wrestling team at Fox Chapel Area High School. He got bigger but not stronger. He couldnt keep up.

He wondered what could be wrong with him.

Several months later, Christman rode the family horse without a saddle. The horse darted off at full speed, knocking him off while tangling his arm in the reins. He told his doctor about other issues the worsening weakness in his arms and legs, his lopsided belly and winged shoulder blade. The doctor sent him to a neurologist.

At age 16, Christman got a diagnosis he didnt know hed been waiting for.

Christman had been born with facioscapulohumeral disease, or FSHD, a rare form of muscular dystrophy that affects about 1 in 8,000 people. A genetic defect causes the overproduction of a protein that kills muscle cells.

The diseases severity can vary widely, from causing total blindness, hearing loss and leg and arm immobility, to people who show few to no symptoms. It has no known cure.

My parents had a really tough time with it, recalled Christman, now a 59-year-old retired business attorney, Whitehall zoning board member and board member of Trib Total Media. For me, I was almost relieved to know: OK, now I know what this is.

I grew up thinking I was a wimp, and I know Im not.

A disease with no cure yet

Christman didnt let the progressive disease get in the way of cultivating a successful professional and personal life.

After marrying his college sweetheart and passing the bar exam, he embarked on a decades-long career in business law while adapting to overcome challenges along the way, from getting around the office and climbing stairs to opening drawers and filing paperwork.

He appreciated the support of his wife, Renee, an elementary school ESL teacher, along with colleagues and strangers who stopped to help him get on the elevator, reach an item on a shelf or get up from a fall. After he opted for a wheelchair, his father drove him from the South Hills to his law firms office every day from 2002 until his retirement in 2015.

But Christman couldnt help feeling misunderstood.

Hed smile politely but felt irked when even close friends asked him, Hows your MS? in reference to an entirely different, nerve-related disease, multiple sclerosis.

A room full of strangers, a room full of friends

For 41 years, Christman never met anyone else who had the same disease as he did. A 2014 event in Boston changed that. At the FSHD Societys Connect Conference, he recalled feeling overcome with emotions when he encountered hundreds of people with varying levels of the FSHD.

The FSHD Society is a nonprofit advocacy and research grant-making group based in Lexington, Mass.

Christman, whos typically an introvert at large gatherings, still gets teary-eyed remembering it.

It was a room full of strangers, and I felt like they were my friends, he said.

Until that cathartic moment, Christman said hes not sure even he realized how isolated hed felt.

My wife is just the best thing that ever happened to me in my life, and I love her dearly but I still felt alone, he said. Everyones experience of the disease is different. But having someone whos shared some of your experiences is a really special thing.

Christman is on a mission to share that gift of connection and empowerment to others across Western Pennsylvania and neighboring states. Last year, he formed Western Pennsylvanias first chapter of the rapidly burgeoning FSHD Society. The organization hopes to accelerate getting promising treatments that could halt the diseases progression to market in as soon as five years.

Christman is searching for more participants and their loved ones to join the group, with at least four dozen believed to be living in the Pittsburgh area.

I want to maybe help other people have that same experience that I had meeting people, said Christman, but also do something to raise money and push this along to find a treatment and a cure.

Christman held the chapters first meeting in June at the National Aviary in Pittsburghs North Side. Seven people attended, including two people with FSHD and their spouses. He expected everyone to want to know the latest research and tips for practical things to make life easier, like how to get an insurance company to approve a more sophisticated, joystick-controlled scooter like his.

Instead, a former coal miner told the group how hard it was for him when he was diagnosed, and a former Aviary employee lamented that her condition forced her to stop working.

All anyone wanted was to talk, Christman said. It was all about sharing.

If you really loved her, you wouldnt marry her

Christman sees the group as a chance for people to discuss things that those who dont know of the disease cant relate to, including its emotional and psychological toll.

Like how his wifes parents reacted when he proposed.

They went on a campaign to stop her, Christman said. They were worried that I wasnt going to be able to support her, and that she was going to have a terrible life. They got me aside and said if I really loved her, I wouldnt marry her.

The week of the wedding, Renees parents called and asked to attend, and did.

They never said anything again, and theyve since apologized, said Christman, adding hes gotten along well with his in-laws ever since. They know they were wrong.

At a recent FSHD event, Christman met a man who feared his children would think less of him for having the disease. Christmans now-adult son reassured the man that wouldnt be the case, that to his kids hed just be dad.

Christman said he may not have been able to play catch, but he made plenty of time to be actively involved in the lives of his three children and never felt like he let them down because of his condition. One of his daughters is a registered nurse, the second is a Hasbro engineer. His son is a teacher.

Theres a 50/50 chance of passing on the gene to a child. But some people have the disease and show few or no symptoms. Christman hasnt identified anyone in his family known to have it.

As a lawyer, Christman sometimes wondered whether his visible physical handicap impacted his clients perception of his mental capabilities.

He wasnt sure whether colleagues thought of him as overly grumpy because of partial facial muscle loss that gives him a half-frown resting face and slightly crooked smile. Hes grateful he hasnt lost his ability to smile, like many people with FSHD do.

Finding patients, expediting treatments

Once the disease gets too far along, the muscles disappear, and theyre replaced by, essentially, scar tissue, said Dr. Paula Clemens, Christmans UPMC neurologist. Once that happens, theres not really a lot of hope in treatments, unless you were to come up with a treatment that would make new muscle, such as by using stem cells an idea thats still a long way from materializing.

The FSHD Society is hoping to expedite the approval of a pill that could stop the disease from getting worse. Formed in 1991 by two patients who have FSH muscular dystrophy, the FSHD Society has focused primarily on raising money for research.

In 2014, newly hired CEO Mark Stone decided that to help expedite the development and approval of newly emerging treatment options, they needed to form local chapters in as many places as possible and get more patients involved and aware of clinical trials.

An estimated 40,000 Americans live with FSHD. But the society is only aware of about 3,500 of them. People may be living with it and not have a formal diagnosis, either because they havent sought one or their doctors havent recognized it.

This is a disease where youve got to also have a very active community, branch coordinator Beth Johnston said, so that if treatments do come to light, they do get to people and you have a disease community who can support it.

The society now has 48 local chapters in 24 states. Its goal is to raise $5 million toward treatment efforts this year.

In addition to providing education and support groups, the society is working directly with medical researchers and officials at the Food and Drug Administration to lobby for expediting clinical trials that appear promising.

Theyre helping us to understand how to accelerate the process that they have in order to get the drugs on the market, Johnston said. Weve got to activate our community. This is such a critical time in therapy development, its super important.

You just adapt

Christman continues to struggle with some tasks on a daily basis, but he has managed to work around his limitations.

You just adapt, he said.

These days, his wife helps him shower and get dressed.

His dad, 85, still drives him to Giant Eagle.

He loves using his iPad and other devices that are operated via voice control, since he has trouble punching keyboards or touch screens with more than one finger. He has a hard time lifting his hands, so hell lean in to do so instead. He can move his right leg to the side, but cant extend it forward.

Alexa, tell Delta to pour one cup water, hell say to the Amazon device beside the kitchen sink that controls the hard-to-reach faucet.

Hes thankful for the work of Carnegie Mellon University students who helped to build him a special tool to use the oven.

A few months ago, Christman and his wife completed a full kitchen renovation that includes an oven with a door that opens sideways as opposed to outward, plenty of reachable cupboard space and a special pull-out feature for him to use his Kitchen Aid mixer.

He has a passion for cooking, especially baking bread. His Whitehall homes bookshelves are stocked with titles like The Bread Bakers Guide, Baking with Julia, Bernard Claytons New Complete Book of Breads and, for meals with an extra kick, The Sriracha Cookbook.

I love it when he cooks dinner with me, said Renee Christman, recalling a recent meal featuring her husbands homemade pizza crust.

In addition to his municipal and board roles, Christman enjoys taking courses through the Osher Lifelong Learning Institute at CMU. Some of his favorites so far include the masters of architecture, the role of food in history, psychology of decision-making and a course on cybercurrency. Hes participating in a CMU pilot project to build more accessible video games.

Even though its getting tougher, hes determined to do tasks like putting on his own coat for as long as he can.

My theory is, if I just let someone else do it all the time, Im not going to be able to do it anymore, Christman said.

But Christman said hes also getting better at accepting help when he needs it. He regrets delaying getting a wheelchair for years, only to realize how much more freedom it gave him.

I want to empower patients, because a lot of people dont know a lot about their disease and whats happening to them, he said. They want to learn and be with people who have gone through similar things. They want to tell their story.

The next meeting of the FSHD Societys Western Pennsylvania chapter is scheduled for 1 to 3 p.m. April 5 at the Carnegie Library branch in Pittsburghs Squirrel Hill neighborhood. For more information, go to FSHDSociety.org, email WesternPAChapter@fshdsociety.org or visit the group on Facebook.

Natasha Lindstrom is a Tribune-Review staff writer. You can contact Natasha at 412-380-8514, nlindstrom@tribweb.com or via Twitter .

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Retired attorney with rare muscular disease FHSD connects with others and accelerates search for cure - TribLIVE

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